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https://wiki.oroboros.at/index.php?title=Bastos_Sant%27Anna_Silva_2018_Life_Sciences_Meeting_2018_Innsbruck_AT&diff=161707
Bastos Sant'Anna Silva 2018 Life Sciences Meeting 2018 Innsbruck AT
2018-08-28T07:01:39Z
<p>Kandolf Georg: Kandolf Georg moved page Bastos Sant'Anna Silva AC 2018 Life Sciences Meeting 2018 Innsbruck AT to Bastos Sant'Anna Silva 2018 Life Sciences Meeting 2018 Innsbruck AT</p>
<hr />
<div>{{Abstract<br />
|title=Effect of cell-permeable succinate and malonate prodrugs on mitochondrial respiration in prostate cancer cells.<br />
|authors=Sant'Anna-Silva ACB, Elmer E, Meszaros AT, Gnaiger E<br />
|year=2018<br />
|event=Life Sciences Meeting 2018 Innsbruck AT<br />
|abstract=Succinate is a substrate mainly metabolized to fumarate in mitochondria by succinate dehydrogenase (SDH) or Complex II. SDH is located at the inner mitochondrial membrane, coupling the oxidation of succinate to fumarate in the tricarboxylic acid cycle (TCA) with electron transfer to ubiquinone. Inhibition or downregulation of SDH leads to an impairment of TCA cycle and respiratory activity, and consequently to accumulation of succinate. This, in turn, transmits an oncogenic signal from mitochondria to the cytosol. Cytosolic succinate inhibits the hypoxia inducible factor 1α (HIF1α) prolyl hydroxylase (PHD) leading to HIF1α stabilization. In this “pseudohypoxic” state angiogenesis and anaerobic metabolism are enhanced, ultimately leading to tumour progression. <br />
<br />
While succinate has essential implications on prostate cancer development, it is difficult to control intracellular succinate concentrations in intact cells due to the low permeability of plasma membranes to the compound. To overcome this limitation, we applied novel plasma membrane-permeable succinate (NV118) and malonate (inhibitor of SDH, NV161) prodrugs in high-resolution respirometry (Oroboros O2k-FluoRespirometer). Mitochondrial respiration was assessed in three cell lines: RWPE-1 (prostate; noncancerous), LNCaP (prostate; cancer), and HEK293T (embryonic kidney; control). <br />
<br />
NV118 (250 µM) stimulated ROUTINE respiration in LNCaP cancer cells by 18% as compared to vehicle (DMSO), while respiration remained unchanged in RWPE-1 (4% increase) and HEK 293T cells, even at higher concentrations of the prodrug. NV161 (66 µM) had no effect on ROUTINE respiration of HEK 293T cells.<br />
<br />
Our results indicate enhanced utilization of external, plasma membrane-permeable succinate in mitochondrial respiration in LNCaP prostate cancer cells but not in control cell lines. The cell-permeable prodrugs offer promising research tools to elucidate the roles of succinate and inhibition of SDH in metabolic reprograming towards a malignant phenotype.<br />
|keywords=mitochondrial respiration, intact cells, cell-permeable succinate,<br />
|editor=[[Sant'Anna-Silva ACB]], [[Kandolf G]],<br />
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck Oroboros, SE Lund Elmer E<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|diseases=Cancer<br />
|tissues=Kidney, Other cell lines, HEK<br />
|preparations=Intact cells, Permeabilized cells<br />
|enzymes=Complex II;succinate dehydrogenase<br />
|topics=Calcium, Substrate<br />
|couplingstates=ROUTINE<br />
|instruments=Oxygraph-2k<br />
|event=Oral<br />
}}<br />
== Affiliations ==<br />
<br />
:::Sant´Anna-Silva ACB(1,2), Elmer E(3), Meszaros AT(1,4), Gnaiger E(1,2)<br />
<br />
::::# Oroboros Instruments, Innsbruck, Austria. - ana.bastos@oroboros.at<br />
::::# Daniel Swarovsky Inst, Medical Univ Innsbruck, Austria<br />
::::# Lund Univ, Sweden<br />
::::# Inst Surgical Research, Univ Szeged, Hungary</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Bastos_Sant%27Anna_Silva_AC_2018_TRANSMIT_Bertinoro_di_Romagna_IT&diff=161663
Bastos Sant'Anna Silva AC 2018 TRANSMIT Bertinoro di Romagna IT
2018-08-27T10:00:48Z
<p>Kandolf Georg: Kandolf Georg moved page Bastos Sant'Anna Silva AC 2018 TRANSMIT Bertinoro di Romagna IT to Bastos Sant'Anna Silva 2018 TRANSMIT Bertinoro di Romagna IT</p>
<hr />
<div>#REDIRECT [[Bastos Sant'Anna Silva 2018 TRANSMIT Bertinoro di Romagna IT]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Bastos_Sant%27Anna_Silva_2018_TRANSMIT_Bertinoro_di_Romagna_IT&diff=161662
Bastos Sant'Anna Silva 2018 TRANSMIT Bertinoro di Romagna IT
2018-08-27T10:00:48Z
<p>Kandolf Georg: Kandolf Georg moved page Bastos Sant'Anna Silva AC 2018 TRANSMIT Bertinoro di Romagna IT to Bastos Sant'Anna Silva 2018 TRANSMIT Bertinoro di Romagna IT</p>
<hr />
<div>{{Abstract<br />
|title=Cellular succinate transport and mitochondrial respiratory function in prostate cancer.<br />
|authors=Sant'Anna-Silva ACB, Klocker H, Weber A, Elmer E, Meszaros AT, Gnaiger E<br />
|year=2018<br />
|event=Course in Cancer Metabolism Bologna IT<br />
|abstract=Succinate dehydrogenase (SDH, mitochondrial Complex II) links the oxidation of succinate and FAD to fumarate and FADH2 in the tricarboxylic acid (TCA) cycle to electron transfer (ET) from FADH2 to ubiquinone in the ET system. Changes in ET capacity through the succinate pathway affect TCA cycle function and cell respiration [1]. In addition, succinate transmits oncogenic signals from mitochondria to the cytosol by stabilization of hypoxia inducible factor 1α. This, in turn, stimulates the expression of genes involved in angiogenesis and anaerobic metabolism [2], finally enabling tumour progression and metastasis. Succinate uptake is enhanced in various cancer cells [3], and its mitochondrial utilisation is increased in permeabilized prostate cancer cells [4].<br />
To decipher the pathophysiological role of succinate in prostate cancer, we measured the plasma membrane permeability for succinate and utilization of external succinate by mitochondria in terms of succinate pathway capacity and kinetic properties in prostate cancer (multiple metastatic origins) and control cell lines.<br />
Respiration in RWPE-1 (prostate; noncancerous), LNCaP (prostate; lymph node metastasis) and DU145 (prostate; brain metastasis) cells was measured using High-Resolution FluoRespirometry (O2k, Oroboros Instruments) and substrate-uncoupler-inhibitor titration (SUIT) protocols developed specifically for the study. To assess succinate utilization in intact cells independent of a plasma membrane succinate transporter, we applied novel plasma membrane-permeable succinate prodrugs (pS) [5]. <br />
In LNCaP cells, transport of external succinate is enhanced through the plasma membrane as compared to the other cell lines, while pS exerted similar effects in all cell lines, suggesting an important regulatory role of the transport mechanism. Furthermore, in LNCaP cells, mitochondria utilize succinate with higher affinity than control cells. Importantly, kinetic measurements demonstrated the most pronounced difference in the affinities in the physiological intracellular succinate concentration range (< 100 µM), underlining its pathophysiological role.<br />
Our results indicate a “succinate phenotype” in LNCaP, with enhanced transport and utilization. As such, succinate is a potential mitochondrial metabolic biomarker in prostate cancer cells. We propose a model in which succinate does not only play a role in the signalling but has a central role in the maintenance of mitochondrial respiration as a fuel substrate.<br />
|keywords=mitochondrial respiration, intact cells, cell-permeable succinate, Prostate cancer, Succinate,<br />
|editor=[[Sant'Anna-Silva ACB]],<br />
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck Oroboros, SE Lund Elmer E<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|diseases=Cancer<br />
|organism=Human<br />
|tissues=Genital, HEK<br />
|preparations=Intact cells, Permeabilized cells<br />
|enzymes=Complex II;succinate dehydrogenase<br />
|topics=Ion;substrate transport, Substrate<br />
|couplingstates=LEAK, ROUTINE, OXPHOS, ET<br />
|pathways=S, ROX<br />
|instruments=Oxygraph-2k, O2k-Protocol<br />
}}<br />
== Affiliations ==<br />
<br />
:::Sant´Anna-Silva ACB(1,2), Klocker H(3), Weber A(3), Elmer E(4), Meszaros AT(1,2), Gnaiger E(1,2)<br />
<br />
::::# Oroboros Instruments, Innsbruck, Austria. - ana.bastos@oroboros.at<br />
::::# Daniel Swarovsky Inst, Medical Univ Innsbruck, Austria<br />
::::# Dept of Urology, Medical Univ Innsbruck, Austria<br />
::::# Dept of Clinical Sciences, Lund Univ, Sweden</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Berger_2016_Nat_Commun&diff=161655
Berger 2016 Nat Commun
2018-08-27T09:26:32Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgäuer M, Staszewski O, Lobner EM, Schöttl T, Giesbertz P, Coleman OI, Prinz M, Weber A, Gerhard M, Klingenspor M, Janssen KP, Heikenwalder M, Haller D (2016) Mitochondrial function controls intestinal epithelial stemness and proliferation. Nat Commun 7:13171.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/27786175 PMID: 27786175 Open Access]<br />
|authors=Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgaeuer M, Staszewski O, Lobner EM, Schoettl T, Giesbertz P, Coleman OI, Prinz M, Weber A*, Gerhard M, Klingenspor M, Janssen KP, Heikenwalder M, Haller D<br />
|year=2016<br />
|journal=Nat Commun<br />
|abstract=Control of intestinal epithelial stemness is crucial for tissue homeostasis. Disturbances in epithelial function are implicated in inflammatory and neoplastic diseases of the gastrointestinal tract. Here we report that mitochondrial function plays a critical role in maintaining intestinal stemness and homeostasis. Using intestinal epithelial cell (IEC)-specific mouse models, we show that loss of HSP60, a mitochondrial chaperone, activates the mitochondrial unfolded protein response (MT-UPR) and results in mitochondrial dysfunction. HSP60-deficient crypts display loss of stemness and cell proliferation, accompanied by epithelial release of WNT10A and RSPO1. Sporadic failure of Cre-mediated Hsp60 deletion gives rise to hyperproliferative crypt foci originating from OLFM4<sup>+</sup> stem cells. These effects are independent of the MT-UPR-associated transcription factor CHOP. In conclusion, compensatory hyperproliferation of HSP60<sup>+</sup> escaper stem cells suggests paracrine release of WNT-related factors from HSP60-deficient, functionally impaired IEC to be pivotal in the control of the proliferative capacity of the stem cell niche.<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=DE Freising Klingenspor M<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|organism=Mouse<br />
|tissues=Endothelial;epithelial;mesothelial cell<br />
|couplingstates=LEAK, OXPHOS<br />
|pathways=S, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Berger_2016_Nat_Commun&diff=161631
Berger 2016 Nat Commun
2018-08-27T07:39:00Z
<p>Kandolf Georg: Created page with "{{Publication |title=Berger E1, Rath E1, Yuan D2, Waldschmitt N1, Khaloian S1, Allgäuer M3, Staszewski O4, Lobner EM1, Schöttl T5, Giesbertz P6, Coleman OI1, Prinz M4,7, Web..."</p>
<hr />
<div>{{Publication<br />
|title=Berger E1, Rath E1, Yuan D2, Waldschmitt N1, Khaloian S1, Allgäuer M3, Staszewski O4, Lobner EM1, Schöttl T5, Giesbertz P6, Coleman OI1, Prinz M4,7, Weber A8, Gerhard M3, Klingenspor M5,9, Janssen KP, Heikenwalder M, Haller D (2016) Mitochondrial function controls intestinal epithelial stemness and proliferation. Nat Commun 7:13171.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/27786175 PMID: 27786175 Open Access]<br />
|authors=Berger E, Rath E, Yuan D, Waldschmitt N1, Khaloian S1, Allgaeuer M3, Staszewski O4, Lobner EM1, Schöttl T5, Giesbertz P6, Coleman OI1, Prinz M4,7, Weber A8, Gerhard M3, Klingenspor M5,9, Janssen KP, Heikenwalder M, Haller D<br />
|year=2016<br />
|journal=Nat Commun<br />
|abstract=Control of intestinal epithelial stemness is crucial for tissue homeostasis. Disturbances in epithelial function are implicated in inflammatory and neoplastic diseases of the gastrointestinal tract. Here we report that mitochondrial function plays a critical role in maintaining intestinal stemness and homeostasis. Using intestinal epithelial cell (IEC)-specific mouse models, we show that loss of HSP60, a mitochondrial chaperone, activates the mitochondrial unfolded protein response (MT-UPR) and results in mitochondrial dysfunction. HSP60-deficient crypts display loss of stemness and cell proliferation, accompanied by epithelial release of WNT10A and RSPO1. Sporadic failure of Cre-mediated Hsp60 deletion gives rise to hyperproliferative crypt foci originating from OLFM4<sub>+</sub> stem cells. These effects are independent of the MT-UPR-associated transcription factor CHOP. In conclusion, compensatory hyperproliferation of HSP60+ escaper stem cells suggests paracrine release of WNT-related factors from HSP60-deficient, functionally impaired IEC to be pivotal in the control of the proliferative capacity of the stem cell niche.<br />
|editor=[[Kandolf G]],<br />
|mipnetlab=AT Innsbruck Oroboros<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|instruments=Oxygraph-2k<br />
|additional=2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Liepins_2018_MiP2018&diff=161606
Liepins 2018 MiP2018
2018-08-24T09:49:15Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]] Mitochondrial and extramitochondrial effects of long-chain acylcarnitines.<br />
|info=[[MiP2018]]<br />
|authors=Liepins E<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] Acylcarnitines have been known for decades as long-chain fatty acid intermediates, but many aspects of their molecular action are still unclear. In our studies we demonstrate that long-chain (LC) acylcarnitines are active metabolites involved in the regulation of energy metabolism. Carnitine palmitoyltransferase 1 (CPT 1)-mediated long-chain acylcarnitine synthesis is a step in mitochondrial FA oxidation, and various mitochondrial disorders that are characterized by incomplete FA oxidation cause the accumulation of long-chain acylcarnitines. In mitochondrial genetic disorders, ischemia and the late stages of heart failure, acylcarnitines accumulate in mitochondria because of a transient or permanent inhibition of FA-dependent oxidative phosphorylation in the mitochondria. Recently we showed that long-chain acylcarnitines, but not acyl-CoAs, accumulate at concentrations that are harmful to mitochondria. Acylcarnitine accumulation in the mitochondrial intermembrane space is a result of increased carnitine palmitoyltransferase 1 (CPT1) and CPT2 activity in ischemic myocardium and it leads to inhibition of oxidative phosphorylation, which in turn induces mitochondrial membrane hyperpolarization and stimulates the production of reactive oxygen species (ROS) in cardiac mitochondria. In the isolated rat heart set-up, the supplementation of perfusion buffer with palmitoylcarnitine before occlusion resulted in a 2-fold increase in the long-chain acylcarnitine content of the heart mitochondria and increased the infarct size (IS) by 33%. A pharmacologically induced decrease in the mitochondrial acylcarnitine content reduced the infarct size by 44%. Similar effect was observed in trimethyllysine dioxygenase (the first enzyme in the biosynthesis pathway of carnitine and acylcarnitne) knock-out mice if compared to wild-type BL6 mice. <br />
<br />
In healthy subjects in the fed state, to facilitate glucose metabolism, the increased concentration of insulin inhibits long-chain acylcarnitine production and subsequent FA metabolism. Disturbances in insulin signalling lead to the inability of insulin to inhibit long-chain acylcarnitine production in the postprandial state. Increase in the content of long-chain acylcarnitine accelerates insulin resistance by impairing Akt phosphorylation at Ser473. <br />
<br />
In conclusion, long-chain acylcarnitine accumulation in ischemic heart is harmful to mitochondria and decreasing the acylcarnitine content via cardioprotective drugs may represent a novel treatment strategy. Moreover, the reduction of acylcarnitine content is an effective strategy to improve cardiac insulin sensitivity.<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling<br />
|area=Genetic knockout;overexpression, mt-Medicine, Pharmacology;toxicology<br />
|diseases=Diabetes<br />
|injuries=Ischemia-reperfusion<br />
|organism=Mouse<br />
|tissues=Heart<br />
}}<br />
== Affiliations ==<br />
:::Latvian Inst Organic Synthesis</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Liepins_2018_MiP2018&diff=161605
Liepins 2018 MiP2018
2018-08-24T09:44:37Z
<p>Kandolf Georg: Created page with "{{Abstract |title=MiPsociety |info=MiP2018 |year=2018 |event=MiP2018 |abstract=Image:MITOEAGLE-lo..."</p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]]<br />
|info=[[MiP2018]]<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling}}<br />
== Affiliations ==<br />
<br />
<br />
== References ==</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Makrecka-Kuka_2018_MiP2018&diff=161604
Makrecka-Kuka 2018 MiP2018
2018-08-24T09:43:09Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MakreckaM.jpg|left|90px|Marina Makrecka-Kuka]] Fatty acid oxidation in brain: from aging to ischemia and sepsis.<br />
|info=[[MiP2018]]<br />
|authors=Makrecka-Kuka M, Doerrier C, Korzh S, Zvejniece L, Gnaiger E, Dambrova M, Liepinsh E<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]] The brain tissues have a high energy demand that is almost exclusively satisfied by metabolizing glucose. Recent studies have demonstrated that also fatty acids are utilized by brain mitochondria. However, the role of fatty acid oxidation (FAO) in brain tissues is still unclear. The aim of the present study was to evaluate the fatty acid oxidation in brain under physiological and pathological conditions.<br />
<br />
Mitochondrial respiration was measured using High-Resolution Fluoespirometry in brain tissue homogenates. The measurements were performed at OXPHOS state using palmitoylcarnitine (PC) or octanoylcarnitine (OC) as substrates. The FAO was evaluated in brain tissues of adult (8 months) and old (20 months) Wistar male rats, as well as in tissues after endothelin-1 (ET-1) induced stroke. In addition, measurements were done using high fat diet-induced insulin resistance and LPS-induced endotoxic shock experimental mice models.<br />
<br />
The measurements in control mice tissues demonstrated that FA-dependent O<sub>2</sub> flux is higher using PC than OC. Moreover, PC, but not OC, inhibits pyruvate metabolism in brain. The PC-dependent O<sub>2</sub> flux was 2.3 times lower in old rat brain compared to adult rat group. In ET-1 induced experimental model of stroke we observed 31% and 66% decrease in PC-dependent O<sub>2</sub> flux 2h and 24h post- ET-1 injection in affected brain area compared to sham control. The high-fat diet for 18 weeks resulted in a 56% reduction of PC-dependent O<sub>2</sub> flux in mice brain. Similarly, the PC-dependent O<sub>2</sub> flux was by 52% lower in LPS-treated mice compared to control group.<br />
<br />
Taking into account FAO biochemical pathway and obtained results, the measurements using PC are more straight-forward to characterize FAO in mitochondria. All studied conditions induced an inhibition of FAO in brain, indicating that FAO and availability of FA metabolites could regulate physiological process as well as play a significant role in the development of neurological disorders. Targeting FAO and availability of FA metabolites provide a novel therapeutic approach for treatment of neuropathological states.<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
|mipnetlab=LV Riga Makrecka-Kuka M, AT Innsbruck Oroboros<br />
}}<br />
{{Labeling<br />
|area=Exercise physiology;nutrition;life style<br />
|diseases=Aging;senescence, Neurodegenerative, Sepsis<br />
|injuries=Ischemia-reperfusion<br />
|organism=Mouse, Rat<br />
|tissues=Nervous system<br />
|preparations=Homogenate<br />
|topics=Fatty acid<br />
|couplingstates=OXPHOS<br />
|pathways=F<br />
}}<br />
== Affiliations ==<br />
:::Makrecka-Kuka Marina(1), Doerrier C(2), Korzh S(1), Zvejniece L(1), Gnaiger E(2,3), Dambrova M(1), Liepinsh E(1)<br />
<br />
::::#Latvian Inst Organic Synthesis, Riga, Latvia. - makrecka@farm.osi.lv<br />
::::#Oroboros Instruments, Innsbruck, Austria<br />
::::#Medical Univ Innsbruck, Austria<br />
<br />
<br />
== Acknowledgments ==<br />
This study was supported by “Post-doctoral Research Aid” programme project Nr.1.1.1.2/VIAA/1/16/246.</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Stelfa_2018_MiP2018&diff=161603
Stelfa 2018 MiP2018
2018-08-24T09:34:50Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]] Neuroprotective compound R-phenibut protects brain mitochondria against anoxia-reoxygenation damage ''in vitro''.<br />
|info=[[MiP2018]]<br />
|authors=Vikmane G, Makrecka-Kuka M, Zvejniece L, Svalbe B, Vavers E, Kupats E, Dambrova M<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
R-phenibut ((3R)-phenyl-4-aminobutyric acid) is a CNS active drug, weak agonist of GABA-B receptors and ligand of α2-δ subunit of voltage-dependent calcium channels, and is clinically used due to its anxiolytic and nootropic effects. Our recent studies show that R-phenibut possesses neuroprotective activity in experimental models of stroke and traumatic brain injury. The preservation of mitochondrial function is essential for normal brain functioning and favourable neurological outcomes after cerebral ischemia. The aim of the present study was to evaluate the effects of R-phenibut on mitochondrial functionality in ''in vitro'' model of anoxia-reoxygenation.<br />
<br />
The acute effects of R-phenibut on anoxia-reoxygenation-induced mitochondrial damage were studied using Wistar rat brain homogenate. The respiration measurements with simultaneous H<sub>2</sub>O<sub>2</sub>/O flux detection were performed in MiR05Cr buffer solution using [[High-Resolution FluoRespirometry]] (Oroboros Instruments, Innsbruck, Austria) as described previously [1]. To induce anoxia, respiration of sample was stimulated by the addition of succinate with rotenone and ADP and preparation was left to consume all O<sub>2</sub> in respiratory chamber (within 10-20 min), thereby reaching an anoxic state. After 30 min of anoxia, vehicle or R-phenibut at a concentration of 0.5 µg/mlwas added and O<sub>2</sub> was reintroduced to the chamber by opening the chamber to achieve reoxygenation. After 8 min, the chamber was closed and O<sub>2</sub> flux monitored for additional 2 min. The effect of anoxia-reoxygenation on mitochondrial function was calculated as a difference between values at normoxia and after anoxia-reoxygenation expressed as percentage of normoxic values.<br />
<br />
Anoxia-reoxygenation induced a significant 1.5-fold increase in H<sub>2</sub>O<sub>2</sub> production rate and H<sub>2</sub>O<sub>2</sub>/O flux ratio in the vehicle control group. The addition of R-phenibut at a concentration of 0.5 µg/ml significantly decreased H<sub>2</sub>O<sub>2</sub> production rate and H<sub>2</sub>O<sub>2</sub>/O flux ratio after anoxia-reoxygenation. Overall, addition of R-phenibut prevented anoxia-reoxygenation-induced increase in H<sub>2</sub>O<sub>2</sub> production and H<sub>2</sub>O<sub>2</sub>/O ratio by 45% and 38%, respectively.<br />
<br />
In conclusion, R-phenibut protects brain mitochondria from anoxia-reoxygenation-induced damage, and this mechanism might underlie the anti-ischemic effects of R-phenibut in stroke and traumatic brain injury models.<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
|mipnetlab=LV Riga Makrecka-Kuka M<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|injuries=Ischemia-reperfusion, Oxidative stress;RONS<br />
|organism=Rat<br />
|tissues=Nervous system<br />
|preparations=Homogenate<br />
|couplingstates=OXPHOS<br />
|pathways=S<br />
|instruments=Oxygraph-2k, O2k-Fluorometer<br />
}}<br />
== Affiliations ==<br />
:::Vikmane G(1,2), Makrecka-Kuka M(1), Zvejniece L(1), Svalbe B(1), Vavers E(1,3), Kupats E(1,3), Dambrova M(1,3)<br />
<br />
::::#Latvian Inst Organic Synthesis<br />
::::#Latvia Univ Life Sciences Technologies<br />
::::#Riga Stradins Univ, Riga, Latvia. - gundega@farm.osi.lv<br />
<br />
<br />
== References ==<br />
:::#Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38.</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Makrecka-Kuka_2018_MiP2018&diff=161602
Makrecka-Kuka 2018 MiP2018
2018-08-24T09:33:18Z
<p>Kandolf Georg: Created page with "{{Abstract |title=Marina Makrecka-Kuka |info=MiP2018 |year=2018 |event=MiP2018 |abstract=Image:MITOEAGLE-logo.jpg|left|100px|link=http:..."</p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MakreckaM.jpg|left|90px|Marina Makrecka-Kuka]]<br />
|info=[[MiP2018]]<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling}}<br />
== Affiliations ==<br />
<br />
<br />
== References ==</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Stelfa_2018_MiP2018&diff=161601
Stelfa 2018 MiP2018
2018-08-24T09:31:22Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]] Neuroprotective compound R-phenibut protects brain mitochondria against anoxia-reoxygenation damage ''in vitro''.<br />
|info=[[MiP2018]]<br />
|authors=Vikmane G, Makrecka-Kuka M, Zvejniece L, Svalbe B, Vavers E, Kupats E, Dambrova M<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
R-phenibut ((3R)-phenyl-4-aminobutyric acid) is a CNS active drug, weak agonist of GABA-B receptors and ligand of α2-δ subunit of voltage-dependent calcium channels, and is clinically used due to its anxiolytic and nootropic effects. Our recent studies show that R-phenibut possesses neuroprotective activity in experimental models of stroke and traumatic brain injury. The preservation of mitochondrial function is essential for normal brain functioning and favourable neurological outcomes after cerebral ischemia. The aim of the present study was to evaluate the effects of R-phenibut on mitochondrial functionality in ''in vitro'' model of anoxia-reoxygenation.<br />
<br />
The acute effects of R-phenibut on anoxia-reoxygenation-induced mitochondrial damage were studied using Wistar rat brain homogenate. The respiration measurements with simultaneous H<sub>2</sub>O<sub>2</sub>/O flux detection were performed in MiR05Cr buffer solution using [[High-Resolution FluoRespirometry]] (Oroboros Instruments, Innsbruck, Austria) as described previously [1]. To induce anoxia, respiration of sample was stimulated by the addition of succinate with rotenone and ADP and preparation was left to consume all O<sub>2</sub> in respiratory chamber (within 10-20 min), thereby reaching an anoxic state. After 30 min of anoxia, vehicle or R-phenibut at a concentration of 0.5 µg/mlwas added and O<sub>2</sub> was reintroduced to the chamber by opening the chamber to achieve reoxygenation. After 8 min, the chamber was closed and O<sub>2</sub> flux monitored for additional 2 min. The effect of anoxia-reoxygenation on mitochondrial function was calculated as a difference between values at normoxia and after anoxia-reoxygenation expressed as percentage of normoxic values.<br />
<br />
Anoxia-reoxygenation induced a significant 1.5-fold increase in H<sub>2</sub>O<sub>2</sub> production rate and H<sub>2</sub>O<sub>2</sub>/O flux ratio in the vehicle control group. The addition of R-phenibut at a concentration of 0.5 µg/ml significantly decreased H<sub>2</sub>O<sub>2</sub> production rate and H<sub>2</sub>O<sub>2</sub>/O flux ratio after anoxia-reoxygenation. Overall, addition of R-phenibut prevented anoxia-reoxygenation-induced increase in H<sub>2</sub>O<sub>2</sub> production and H<sub>2</sub>O<sub>2</sub>/O ratio by 45% and 38%, respectively.<br />
<br />
In conclusion, R-phenibut protects brain mitochondria from anoxia-reoxygenation-induced damage, and this mechanism might underlie the anti-ischemic effects of R-phenibut in stroke and traumatic brain injury models.<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|injuries=Ischemia-reperfusion, Oxidative stress;RONS<br />
|organism=Rat<br />
|tissues=Nervous system<br />
|preparations=Homogenate<br />
|couplingstates=OXPHOS<br />
|pathways=S<br />
|instruments=Oxygraph-2k, O2k-Fluorometer<br />
}}<br />
== Affiliations ==<br />
:::Vikmane G(1,2), Makrecka-Kuka M(1), Zvejniece L(1), Svalbe B(1), Vavers E(1,3), Kupats E(1,3), Dambrova M(1,3)<br />
<br />
::::#Latvian Inst Organic Synthesis<br />
::::#Latvia Univ Life Sciences Technologies<br />
::::#Riga Stradins Univ, Riga, Latvia. - gundega@farm.osi.lv<br />
<br />
<br />
== References ==<br />
:::#Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38.</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Stelfa_2018_MiP2018&diff=161599
Stelfa 2018 MiP2018
2018-08-24T09:21:16Z
<p>Kandolf Georg: Created page with "{{Abstract |title=MiPsociety |info=MiP2018 |year=2018 |event=MiP2018 |abstract=Image:MITOEAGLE-lo..."</p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]]<br />
|info=[[MiP2018]]<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling}}<br />
== Affiliations ==<br />
<br />
<br />
== References ==</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Britto_2018_BMC_Biol&diff=161585
Britto 2018 BMC Biol
2018-08-24T06:23:06Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Britto FA, Cortade F, Belloum Y, Blaquière M, Gallot YS, Docquier A, Pagano AF, Jublanc E, Bendridi N, Koechlin-Ramonatxo C, Chabi B, Francaux M, Casas F, Freyssenet D, Rieusset J, Giorgetti-Peraldi S, Carnac G, Ollendorff V, Favier FB (2018) Glucocorticoid-dependent ''REDD1'' expression reduces muscle metabolism to enable adaptation under energetic stress. BMC Biol 16:65.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29895328 PMID: 29895328 Open Access]<br />
|authors=Britto FA, Cortade F, Belloum Y, Blaquiere M, Gallot YS, Docquier A, Pagano AF, Jublanc E, Bendridi N, Koechlin-Ramonatxo C, Chabi B, Francaux M, Casas F, Freyssenet D, Rieusset J, Giorgetti-Peraldi S, Carnac G, Ollendorff V, Favier FB<br />
|year=2018<br />
|journal=BMC Biol<br />
|abstract=Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a component of energy stress responses.<br />
<br />
Unexpectedly, we show here that REDD1 instead limits muscle loss during energetic stresses such as hypoxia and fasting by reducing glycogen depletion and AMPK activation. Indeed, we demonstrate that REDD1 is required to decrease O<sub>2</sub> and ATP consumption in skeletal muscle via reduction of the extent of mitochondrial-associated endoplasmic reticulum membranes (MAMs), a central hub connecting energy production by mitochondria and anabolic processes. In fact, REDD1 inhibits ATP-demanding processes such as glycogen storage and protein synthesis through disruption of the Akt/Hexokinase II and PRAS40/mTORC1 signaling pathways in MAMs. Our results uncover a new REDD1-dependent mechanism coupling mitochondrial respiration and anabolic processes during hypoxia, fasting, and exercise.<br />
<br />
Therefore, REDD1 is a crucial negative regulator of energy expenditure that is necessary for muscle adaptation during energetic stresses. This present study could shed new light on the role of REDD1 in several pathologies associated with energetic metabolism alteration, such as cancer, diabetes, and Parkinson's disease.<br />
|keywords=Energy expenditure, Exercise, Fasting, Hypoxia, MAMs, Metabolism, Mitochondria, Skeletal muscle, mTOR<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=FR Montpellier Wrutniak-Cabello C<br />
}}<br />
{{Labeling<br />
|area=Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style<br />
|organism=Mouse<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized cells, Isolated mitochondria<br />
|couplingstates=LEAK, OXPHOS<br />
|pathways=F, N, NS, Other combinations<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=AT_Innsbruck_Oroboros&diff=161421
AT Innsbruck Oroboros
2018-08-23T15:02:20Z
<p>Kandolf Georg: </p>
<hr />
<div>{{O2k-Network Lab<br />
|institution=[[Image:Logo OROBOROS INSTRUMENTS.jpg|left|100px|link=http://www.oroboros.at|Oroboros]]<br />
Oroboros Instruments Corp<br />
<br />
<br />
'''[[High-Resolution FluoRespirometry]]'''<br />
<br />
'''[[Oroboros O2k |O2k – Mitochondrial and cell research]]'''<br />
|address=[mailto:instruments@oroboros.at instruments@oroboros.at]<br />
<br />
Schöpfstraße 18<br />
|area code=A-6020<br />
|city=Innsbruck<br />
|country=Austria<br />
|weblink=[[OROBOROS INSTRUMENTS]], [[Bioblast]]<br />
|Contact=Oroboros, Gnaiger Erich<br />
|MiPNetLab=Bastos Sant'Anna Silva Ana Carolina, Beno Marija, Di Marcello Marco, Doerrier Carolina, Erhart Verena, Garcia e Souza Luiz Felipe, Garipi Enis, Gradl Lukas, Gradl Philipp, Haider Markus, Harrison David K, Hunger Miriam, Iglesias-Gonzalez Javier, Kandolf Georg, Komlodi Timea, Kranewitter Sabine, Krumschnabel Gerhard, Laner Verena, Leman Geraldine, Liebscher Gudrun, Meszaros Andras, Nirschl Lisa, Passrugger Manuela, Perez Valencia Juan Alberto, Pranger Florian, Plangger Mario, Radis Christina, Schmarl Johannes, Volani Chiara, Weber Anja, Zhang Feiyuan<br />
|Team previous=Bader Helga, Burtscher Johannes, Capek Ondrej, Chang Shao-Chiang, Davidikova Sarka, Drinnan Michael, Eigentler Andrea, Fasching Mario, Gasser Juliane, Gellerich Frank N, Hansl Marielle, Heidler Juliana, Hiller Elisabeth, Hoppel Florian, Horvath Gergo, Kuznetsov Andrey V, Lamberti Giorgia, Lassnig Barbara, Lemieux Helene, Martic Ines, Mendez Gabriela, Neves Pedro, Pesta Dominik, Renner-Sattler Kathrin, Rieger Gunde, Scandurra Francesca M, Schoepf Bernd, Sigl Reinhard, Simonovik Biljana, Steinlechner-Maran Rosmarie, Subarsky Patrick, Sumbalova Zuzana, Wiethuechter Anita, Wohlfarter Yvonne<br />
|Status=[[Power-O2k| '''The Power-O2k''']] 1992-<br />
|info=[[Bioblast 2012]], [[O2k-Workshops]]<br />
|keyword=[[High-Resolution FluoRespirometry]], [[Oroboros O2k]], [[Gentle Science]]<br />
}}<br />
== The O2k-Team ==<br />
<br />
::::* The [[Oroboros_contact| O2k-Team]] is presented here in terms of the staff of Oroboros Instruments, collaborators in the [[AT_Innsbruck_Gnaiger E|Mitochondrial Physiology Research Group]] of Erich Gnaiger at the Medical University of Innsbruck, and company partners.<br />
::::* [[Gradl P|Philipp Gradl]] is the CEO of an independent company partner (WGT-Elektronik) of the O2k-Team, cooperating in the development of the O2k since 2001, responsible for the electronics, mechanics, and production.<br />
::::* [[Gradl L|Lukas Gradl]] is an independent company partner of the O2k-Team, cooperating in the development of [[DatLab]] since 2001.<br />
<br />
<br />
== ''MitFit'' ==<br />
::::* [[K-Regio MitoFit|Partner of K-Regio MitoFit]]<br />
::::* See also [[AT_Innsbruck_Gnaiger E]]<br />
<br />
<br />
== Expeditions: science and adventure ==<br />
::::* [[AT_Innsbruck_Gnaiger_E#Expeditions:_science_and_adventure|Studies at high latitude and high altitude]]<br />
::::* [[The world as a laboratory|Expeditions with the O2k]]<br />
<br />
<br />
== Gentle Science Shapes the World == <br />
::::* As an integral component of our company's Corporate Social Responsibility, Oroboros Instruments supports the concept of [[Gentle_Science]]. ''Think about your paper – reduce the pressure to print''.<br />
::::* [[Oroboros Events]] are listed as [[MitoGlobal Events]].</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Unterweger_J&diff=161420
Unterweger J
2018-08-23T15:00:24Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Person<br />
|lastname=Unterweger<br />
|firstname=Jasmin<br />
|institution=:::::::::::::::[[File:UnterwegerJ.JPG|right|150px|Jasmin Unterweger]] <br />
'''Medizinische Universität Innsbruck'''<br />
:::Department of Surgery<br />
|city=Innsbruck<br />
|country=Austria<br />
}}<br />
{{Labelingperson}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Unterweger_Jasmin&diff=161415
Unterweger Jasmin
2018-08-23T14:32:59Z
<p>Kandolf Georg: Kandolf Georg moved page Unterweger Jasmin to Unterweger J</p>
<hr />
<div>#REDIRECT [[Unterweger J]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Unterweger_J&diff=161414
Unterweger J
2018-08-23T14:32:59Z
<p>Kandolf Georg: Kandolf Georg moved page Unterweger Jasmin to Unterweger J</p>
<hr />
<div>{{Person<br />
|lastname=Unterweger<br />
|firstname=Jasmin<br />
|institution=:::::::::::::::[[File:UnterwegerJ.JPG|right|150px|Jasmin Unterweger]] <br />
'''Medizinische Universität Innsbruck'''<br />
|city=Innsbruck<br />
|country=Austria<br />
}}<br />
{{Labelingperson}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Oroboros_contact&diff=161413
Oroboros contact
2018-08-23T14:32:26Z
<p>Kandolf Georg: </p>
<hr />
<div><br />
{{Template:OROBOROS banner}}<br />
<br />
{{Template:OROBOROS navigation line}} [[File:PEND8936mod.jpg|right|570px|Oroboros 25 years - 2017-12-12|link=Oroboros 25 years - since 1992]] [[File:O2k-Fluorometer Rollup.jpg|left|300px|O2k-Fluorometer|link=O2k-FluoRespirometer]] <big>'''Oroboros Instruments Corp'''</big><br />
<br />
<big>'''[[About_Oroboros|Mitochondria and cell research]]'''</big><br />
<br />
Schöpfstraße 18<br />
<br />
A-6020 Innsbruck, Austria<br />
<br />
Tel: +43 512 566796<br />
<br />
Fax: +43 512 566796 20<br />
<br />
Email: [mailto:instruments@oroboros.at| instruments@oroboros.at]<br />
<br />
Commercial Register No: 193145m<br/> <br/> <br/> &nbsp;» Join us on Facebook: [https://www.facebook.com/pages/Oroboros-Instruments/514605351942009?ref=hl| Oroboros Instruments]<br/> &nbsp;<br />
<br />
<big>'''High-Resolution FluoRespirometry'''</big><br/> <br/> '''[[O2k-technical_support_and_open_innovation|O2k-technical support and open innovation]]''':<br />
<br />
Email [mailto:support@oroboros.at| support@oroboros.at]<br/> <br/> <br/> ''We do not develop instruments to be in business with science,''<br />
<br />
''but we are in business to develop instruments and promote '''[[Gentle_Science|Gentle Science]]'''.''<br />
<br />
<br/><br />
'''We are currently looking for an applicant with relevant educational qualification and work experience to fill the position of <big>[http://wiki.oroboros.at/index.php/Oroboros_open_positions Sale and Marketing Assistant]</big>.'''<br />
<br />
<br/><br />
----<br />
&nbsp;<br />
<br />
:<br />
::<br />
:::<br />
::::<big>'''[[MiPNet14.10_O2k-Top_10|» Top 10 reasons]] and more - making us special'''</big> <br />
<br />
&nbsp;<br />
<br />
*Located in Austria ([[Oroboros_location|» map]]), we distribute the O2k world-wide. <br />
*We are specialists in mitochondrial physiology and instrumental development. <br />
*With an instrument and concept, we connect scientists:&nbsp;» [[O2k-Network|O2k-Network]] <br />
<br />
&nbsp;<br />
<br />
<br />
[[File:OROBOROS-solo.png|left|50px|link=http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS Oroboros]]<br />
<br />
:<br />
::<br />
:::<br />
::::[[Oroboros_logo|Oroboros logo]] - an archetypical symbol of a dragon forming a circle, where “creation and the created become one in an inseparable process” ([[MiPArt Gallery|MiP''Art'']]). <br />
<br />
&nbsp;<br />
<br />
__TOC__<br />
<br />
== The Oroboros team ==<br />
<br />
:<br />
::<br />
:::<big>'''Quality is our mission - science our passion: Cooperation and feedback in science'''</big> <br />
<br />
:<br />
::<br />
:::<br />
::::'''Languages:''' The international company language of Oroboros Instruments is English. For scientific support, the Oroboros-Team can provide you with help in the following languages: <br />
::::*English (all) and German (with an Austrian touch). <br />
::::*In alphabetical order: Croatian, English, German, Hungarian, Italian, Mandarin, Portuguese, Spanish. <br />
::::*Of course, the national languages are spoken by our distributors in [[CN Shanghai Zenda|China]], [[JP Tokyo Sanyo|Japan]], [[KR_Seoul_Mymed|Republic of Korea]], [[TW_Taoyuan_Sunpoint|Taiwan]]. <br />
<br />
<br />
<br />
<br/><br />
<br />
{| style="color: black; width: 90%"<br />
|-<br />
| style="text-align: center; background-color: #ffffff" | '''Oroboros operations team'''<br />
| style="text-align: center; background-color: #EFF5FB" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:Gnaiger Erich.jpg|'''[[Gnaiger E|Erich Gnaiger]]''', PhD. - Founder and CEO of Oroboros Instruments<br />
Image:Gnaiger Andrea.jpg|'''[[Gnaiger A |Andrea Gnaiger]]''', Mag. - Chief financial officer<br />
Image:VG.jpg|'''[[Laner V|Verena Laner]]''', Mag.biol. - Chief operating officer<br />
Image:KranewitterS.JPG|'''[[Kranewitter S|Sabine Kranewitter]]''', MSc. - Chief sales officer<br />
Image:ZhangF.jpg|'''[[Zhang Feiyuan|Feiyuan Zhang]]''' - Chief marketing officer<br />
Image:DoerrierC.JPG|'''[[Doerrier C|Carolina Doerrier]]''', PhD. - Chief scientific officer<br />
Image:MeszarosA.JPG|'''[[Meszaros A|András Mészáros]]''', MD., PhD. - Chief research officer<br />
</gallery><br />
|-<br />
| style="text-align: center; background-color: #EFF5FB" | '''Oroboros project management'''<br />
| style="text-align: center; background-color: #ffffff" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:VG.jpg|'''[[Laner V|Verena Laner]]''', Mag.biol. - Chief operating officer<br />
Image:PrangerF.JPG|'''[[Pranger F|Florian Pranger]]''', PhD. - R&D, Project manager<br />
Image:BenoM.JPG|'''[[Beno Marija|Marija Beno]]''' - Project manager<br />
Image:NirschlL.jpg|'''[[Nirschl L|Lisa Nirschl]]''', BA - Administrative assistant<br />
</gallery><br />
|-<br />
| style="text-align: center; background-color: #ffffff" | '''Oroboros sales & marketing'''<br />
| style="text-align: center; background-color: #EFF5FB" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:KranewitterS.JPG|'''[[Kranewitter S|Sabine Kranewitter]]''', MSc. - Chief sales officer<br />
Image:ZhangF.jpg|'''[[Zhang F|Feiyuan Zhang]]''' - Chief marketing officer<br />
Image:SchmarlJ.JPG|'''[[Schmarl J|Johannes Schmarl]]''', Mag. - Sales assistant<br />
Image:Verena_M.jpg|'''[[Erhart V|Verena Erhart]]''', Mag. - Sales assistant<br />
Image:KandolfG.JPG|'''[[Kandolf G|Georg Kandolf]]''', Mag. MSc. - Marketing assistant<br />
Image:RadisC.jpg|'''[[Radis C|Christina Radis]]''', BSc. - Administrative assistant<br />
Image:PlanggerM.JPG|'''[[Plangger M|Mario Plangger]]''' - Marketing assistant<br />
</gallery><br />
|-<br />
| style="text-align: center; background-color: #EFF5FB" | '''Oroboros research & development'''<br />
| style="text-align: center; background-color: #ffffff" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:DoerrierC.JPG|'''[[Doerrier C|Carolina Doerrier]]''', PhD. - Chief scientific officer<br />
Image:MeszarosA.JPG|'''[[Meszaros A|András Mészáros]]''', MD., PhD. - Chief research officer<br />
Image:Iglesias-GonzalezJ.JPG|'''[[Iglesias-Gonzalez J | Javier Iglesias-Gonzalez]]''', PhD. - Principal Investigator [[MitoFit]]<br />
Image:PerezJ.JPG|'''[[Perez Valencia JA | Juan Perez Valencia]]''', PhD. - PostDoc [[MitoFit]]<br />
Image:KomlodiT.JPG|'''[[Komlodi T|Timea Komlòdi]]''', PhD. candidate - Research assistant<br />
Image:Krumschnabel Gerhard.jpg|'''[[Krumschnabel G|Gerhard Krumschnabel]]''', Univ.-Doz. Mag. PhD. - Science writer<br />
Image:PassruggerM.JPG|'''[[Passrugger M|Manuela Passrugger]]''', BSc. - Biomedical assistant<br />
Image:HungerM.JPG|'''[[Hunger M|Miriam Hunger]]''', PhD. - Scientific assistant<br />
Image:David.jpg|'''[[Harrison DK| David Harrison]]''', Doz., PhD. - Independent scientific consultant <br />
Image:Bastos Sant'Anna Silva AC.jpg|'''[[Bastos Sant'Anna Silva AC|Ana Carolina Bastos Sant'Anna Silva]]''', MSc. - PhD. student [[TRANSMIT]] <br />
Image:GarciaL.JPG|'''[[Garcia e Souza Luiz Felipe|Luiz Felipe Garcia e Souza]]''' - PhD. student [[MitoFit]]<br />
student [[TRANSMIT]]<br />
Image:Di MarcelloM.jpg|'''[[Di Marcello M |Marco Di Marcello]]''', BSc. - Scientific Assistant<br />
Image:GaripiE.JPG| '''[[Garipi Enis]]''', Dr., PhD. student [[TRACT]]<br />
<br />
</gallery><br />
|-<br />
| style="text-align: center; background-color: #ffffff" | '''COST Action [[MitoEAGLE|MitoEAGLE]]'''<br/> [[File:MITOEAGLE-logo.jpg|80px|MitoEAGLE|link=http://www.mitoglobal.org/index.php/MitoEAGLE]]<br />
| style="text-align: center; background-color: #EFF5FB" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:HillerE.JPG|'''[[Hiller E|Elisabeth Hiller]]''' - Grant holder administrative assistant<br />
Image:SchartnerM.jpg|'''[[Schartner M|Melanie Schartner]]''', Student; [http://www.mitoeagle.org/index.php/Management_Committee_MitoEAGLE#Grant_holder_and_COST_officers MitoEAGLE Grant Holder science representative]<br />
</gallery><br />
|-<br />
| style="text-align: center; background-color: #EFF5FB" | '''Collaborations: PhD and diploma students, internships'''<br />
| style="text-align: center; background-color: #ffffff" | &nbsp; <br />
<gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
Image:VolaniC.JPG|'''[[Volani C|Chiara Volani]]''', PhD. student<br />
Image:WeberA.JPG|'''[[Weber A| Anja Weber]]''', Mag., PhD. student<br />
Image:LiebscherG.JPG|'''[[Liebscher G|Gudrun Liebscher]]''', MSc., PhD. student<br />
Image:LemanG.JPG|'''[[Leman G|Géraldine Leman]]''', Postdoctoral researcher<br />
File:Profile-icon-9.png|'''[[Holzknecht M|Max Holzknecht]]''', PhD. student<br />
File:PetitM.jpg|'''[[Petit M|Michele Petit]]''', PhD. student<br />
File:Solmaz.png|'''[[Etemad S|Solmaz Etemad]]''', Postdoctoral researcher<br />
Image:FischerC.JPG|'''[[Fischer C| Christine Fischer]]''', MSc, PhD. student<br />
Image:UnterwegerJ.JPG|'''[[Unterweger J| Jasmin Unterweger]]''', Student<br />
</gallery><br />
<br />
|-<br />
| style="text-align: center; background-color: #ffffff" | '''Visiting scientists'''<br />
| style="text-align: center; background-color: #EFF5FB" | <gallery heights="165px" mode="nolines" perrow="6" widths="192px"><br />
</gallery><br />
|}<br />
<br />
&nbsp;<br />
<br />
== The Oroboros MitoFit Laboratory ==<br />
<center><br />
{| style="color: black; background-color: #ffffff; width: 50%"<br />
|-<br />
| [[File:OROBOROS MitoFit-Lab.jpg|210px|MitoFit Laboratory|link=Oroboros MitoFit Laboratory]]<br />
| [[File:The world as a laboratory.jpg|170px|Science and adventure|link=http://wiki.oroboros.at/index.php/The_world_as_a_laboratory]]<br />
|-<br />
| &nbsp;» '''[[Oroboros_MitoFit_Laboratory|Oroboros MitoFit Laboratory]]'''<br />
| &nbsp;» '''[[Oroboros_MitoFit_lab:_visiting_scientists|Visiting scientists]]'''<br />
|}<br />
</center> <br />
&nbsp;<br />
<br />
== Collaborations & Partners ==<br />
<br />
<br/> '''Collaborations'''<br/> <br/> [[File:O2k-Network.png|left|60px|O2k-Network|link=http://wiki.oroboros.at/index.php/O2k-Network]] [[IT_Verona_Capelli_C|University of Verona]] and '''Oroboros Instruments''':<br/> Research collaboration agreement - Mitochondrial function in blood cell subpopulations of middle aged and older adults.<br/> <br/> <br/> '''Oroboros partners'''<br/> <br/> <br/> <gallery heights="165px" mode="nolines" perrow="3" widths="192px"><br />
Image:Philipp Gradl.jpg|'''[[Gradl P|Philipp Gradl]]''', WGT-Elektronik GmbH & Co KG<br />
Image:Lukas Gradl.jpg|'''[[Gradl L|Lukas Gradl]]''', software security networks<br />
Image:HaiderM.jpg|'''[[Haider M|Markus Haider]]''', PhD, SHTech software development<br />
</gallery><br />
<br />
<br/> <br/> <br/> &nbsp;» ''More details:'' '''[[Oroboros_partners|Our partners]]'''<br />
<br />
<br/> <br/><br />
<br />
&nbsp;<br />
== How to get to our office ==<br />
<br />
{| class="wikitable"<br />
|-<br />
! colspan="6" | Directions<br />
|-<br />
| rowspan="2" | <center>'''Arrival at Innsbruck Airport'''</center> <center>[https://www.google.at/maps/dir/Innsbruck+Klinik/Universität/Schöpfstraße+18,+Innsbruck/@47.2621486,11.3860152,17z/data=!3m1!4b1!4m13!4m12!1m5!1m1!1s0x479d6bef91dcda05:0xcf7304bbf72d84e0!2m2!1d11.386692!2d47.263982!1m5!1m1!1s0x479d6be5d52e7e0d:0x32649fc756aa99d9!2m2!1d11.3893197!2d47.2605308?hl=de See Map.]</center> <br />
| '''Innsbruck Airport''' is located on the outskirts of Innsbruck. Public transport is serviced regularly and the bus to the city takes 15 minutes.<br />
|-<br />
| '''Bus directions:''' At Innsbruck Airport, take '''line F''' (bus; direction: ''Baggersee''), exit at ''Klinik/Universität''. From there, it is a 5-minute-walk to our office (Schöpfstrasse 18). <br />
'''Taxi''' service is available.<br />
<br />
|-<br />
| rowspan="2" | <center>'''Arrival at Innsbruck Main Station'''</center> <center>[https://www.google.at/maps/dir/Bahnhof+Innsbruck,+Südtiroler+Platz,+Innsbruck/Schöpfstraße+18,+Innsbruck/@47.2589948,11.3908318,16z/data=!4m14!4m13!1m5!1m1!1s0x479d6958759109e1:0x2cfa9a3996927dfd!2m2!1d11.4005166!2d47.2634144!1m5!1m1!1s0x479d6be5d52e7e0d:0x32649fc756aa99d9!2m2!1d11.3893197!2d47.2605308!5i2?hl=de See Map.]</center> <br />
| It is a ten-minute walk from Innsbruck Main Station to the Oroboros Office. <br />
'''Taxi''' service is available.<br />
<br />
|}<br />
<br />
&nbsp;<br />
<br />
<br />
== Our visions ==<br />
<br />
{| class="wikitable" style="float:left; margin-right: 50px"<br />
|-<br />
| [[File:Company-of-Scientists logo.jpg|left|100px|Company of Scientists|link=http://www.company-of-scientists.com]]<br />
| Our company of scientists is supported by artists:&nbsp;» [http://www.mipart.at/?MiPArt13-MiP2014 Mitochondrial Physiology Art Gallery - MiPArt]<br />
|-<br />
| [[File:Bioblast-logo-ATPSynthase-Oroboros.png|left|100px|Bioblast wiki by Oroboros|link=Bioblast]]<br />
| '''Oroboros''' and Bioblast: '''[[Bioblast|Bioblast]]''' by [[OROBOROS_INSTRUMENTS|Oroboros Instruments]] is a developing scientific database - and [[Gentle_Science|more]]<br />
|-<br />
| [[File:MitoPedia.jpg|100px|MitoPedia|link=MitoPedia]]<br />
| '''[[MitoPedia|MitoPedia]]''' - high-resolution terminology matching measurements at high-resolution<br />
|-<br />
| [[File:MiPMap Publication.jpg|100px|Publications in the MiPMap|link=MiPMap]]<br />
| '''[[Mitochondr_Physiol_Network|Mitochondr Physiol Network]]''' - the Bioblast Open Access publication series<br />
|-<br />
| [[File:MitoGlobal.jpg|100px|MitoGlobal|link=MitoGlobal]]<br />
| Open innovation - building greater ideas: [[MitoGlobal|MitoGlobal]]<br />
|}<br />
<br />
<br/> [[File:MitoGlobal by Odra Noel.jpg|280px|MiPArt by Odra Noel]]<br />
<br />
:<br />
::<br />
:::<br />
::::More links: <br />
<br />
:<br />
::<br />
:::<br />
::::<br />
:::::[https://www.youtube.com/watch?v=sAErSICW24c&feature=youtu.be » The joy of success is the next step - a video on Oroboros] <br />
::::» [[Gentle_Science|Gentle Science shapes the world]] <br />
::::» [[Gnaiger_2012_Abstract_Bioblast-Gentle_Science|Bioblast-Gentle Science]] <br />
<br />
<br/> <br/> <br/> &nbsp;</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Unterweger_J&diff=161410
Unterweger J
2018-08-23T14:21:21Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Person<br />
|lastname=Unterweger<br />
|firstname=Jasmin<br />
|institution=:::::::::::::::[[File:UnterwegerJ.JPG|right|150px|Jasmin Unterweger]] <br />
'''Medizinische Universität Innsbruck'''<br />
|city=Innsbruck<br />
|country=Austria<br />
}}<br />
{{Labelingperson}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=File:UnterwegerJ.JPG&diff=161409
File:UnterwegerJ.JPG
2018-08-23T14:20:10Z
<p>Kandolf Georg: </p>
<hr />
<div></div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Unterweger_J&diff=161407
Unterweger J
2018-08-23T14:11:42Z
<p>Kandolf Georg: Created page with "{{Person}}"</p>
<hr />
<div>{{Person}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Wilson_2018_Virginia_Tech&diff=161384
Wilson 2018 Virginia Tech
2018-08-22T13:49:29Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=Wilson ZT, Perry JB, Brow DA (2018) High-resolution respirometry of heart mitochondria in healthy and stressed states. Virginia Tech.<br />
|info=[https://vtechworks.lib.vt.edu/handle/10919/84553 VTechWorks]<br />
|authors=Wilson ZT, Perry JB, Brown DA<br />
|year=2018<br />
|event=Virginia Tech<br />
|abstract=Heart disease remains the leading cause of death globally, claiming the lives of nearly 10 million people in 2016. Current standard-of-care therapies for heart disease patients reduce energy demands on the heart but do not treat underlying deficits in cellular energy production. Cardiac mitochondria are primarily responsible for the production of energy in the heart, and targeting dysfunctional mitochondria represents a promising solution to improving the prognosis of heart disease patients. Increased production of reactive oxygen species in heart disease damages mitochondrial function, ultimately decreasing cardiac energy supply. Isolated mitochondria exposed to hydrogen peroxide serves as a heart disease model where the reactive oxygen species damage the respiratory chain, a series of complexes responsible for the actual production of energy. N-acetylcysteine (NAC) is a drug precursor to glutathione, an endogenous antioxidant which reduces reactive oxygen species. In this project, isolated mitochondria are treated with hydrogen peroxide with or without NAC. If NAC is capable of rescuing the respiratory rate, that would suggest that NAC restores mitochondrial energy production in pathological states. If successful, these data would be the first step in determining if incorporation of NAC into heart disease treatment plans could begin to better treat the number of one cause of morbidity/mortality on the planet.<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=US NC Greenville Brown DA<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|diseases=Cardiovascular<br />
|injuries=Temperature<br />
|tissues=Heart<br />
|preparations=Isolated mitochondria<br />
|couplingstates=OXPHOS<br />
|pathways=N<br />
|instruments=Oxygraph-2k<br />
}}<br />
== Affiliations ==<br />
::::Dept Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, USA<br />
<br />
== Figures ==<br />
[[File:Wilson_2018_Virginia_Tech_Poster.jpg|left|400 px]]<br />
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== Acknowledgement ==<br />
Funding for the TOUR Scholars program provided by the Department of Human Nutrition, Foods, and Exercise, the College of Agriculture and Life Sciences, The Obesity Interdisciplinary Graduate Education Program, and the Center for Transformative Research on Health Behaviors, and is under the direction of Dr. Deborah J. Good and Dr. Samantha M. Harden. This research was supported by NIH NHLBI RO1 HL123647.</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Perry_JB&diff=161383
Perry JB
2018-08-22T13:48:30Z
<p>Kandolf Georg: Redirected page to Perry J</p>
<hr />
<div>#REDIRECT[[Perry J]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Scalzo_2018_Physiol_Rep&diff=161380
Scalzo 2018 Physiol Rep
2018-08-22T13:17:01Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Scalzo RL, Knaub LA, Hull SE, Keller AC, Hunter K, Walker LA, Reusch JEB (2018) Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats. Physiol Rep 6:e13754.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29984491 PMID: 29984491 Open Access]<br />
|authors=Scalzo RL, Knaub LA, Hull SE, Keller AC, Hunter K, Walker LA, Reusch JEB<br />
|year=2018<br />
|journal=Physiol Rep<br />
|abstract=Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon-like peptide-1 (GLP-1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP-1 is necessary for adaptation to ET. Twelve-week-old male Wistar rats were randomized (n = 8-12/group) to receive PBS or GLP-1 receptor antagonist (exendin 9-39 (Ex(9-39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9-39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9-39) attenuated acetylcholine-mediated vasodilation, while this response was maintained with Ex(9-39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9-39) (P = 0.057) and was made worse when Ex(9-39) was combined with ET (P = 0.004). ''Ex vivo'' aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9-39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9-39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9-39) (P < 0.02). GLP-1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP-1 is integral to the adaptive vascular response to ET.<br />
|keywords=Aortic strain, Mitochondrial respiration, Vascular stiffness<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
|mipnetlab=US CO Denver Schauer I<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|organism=Rat<br />
|tissues=Heart<br />
|preparations=Permeabilized tissue<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=F, NS, Other combinations<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Scalzo_2018_Physiol_Rep&diff=161379
Scalzo 2018 Physiol Rep
2018-08-22T13:16:18Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Scalzo RL, Knaub LA, Hull SE, Keller AC, Hunter K, Walker LA, Reusch JEB (2018) Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats. Physiol Rep 6:e13754.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29984491 PMID: 29984491 Open Access]<br />
|authors=Scalzo RL, Knaub LA, Hull SE, Keller AC, Hunter K, Walker LA, Reusch JEB<br />
|year=2018<br />
|journal=Physiol Rep<br />
|abstract=Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon-like peptide-1 (GLP-1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP-1 is necessary for adaptation to ET. Twelve-week-old male Wistar rats were randomized (n = 8-12/group) to receive PBS or GLP-1 receptor antagonist (exendin 9-39 (Ex(9-39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9-39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9-39) attenuated acetylcholine-mediated vasodilation, while this response was maintained with Ex(9-39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9-39) (P = 0.057) and was made worse when Ex(9-39) was combined with ET (P = 0.004). ''Ex vivo'' aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9-39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9-39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9-39) (P < 0.02). GLP-1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP-1 is integral to the adaptive vascular response to ET.<br />
|keywords=Aortic strain, Mitochondrial respiration, Vascular stiffness<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
|mipnetlab=US CO Denver Schauer I<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|organism=Mouse<br />
|tissues=Heart<br />
|preparations=Permeabilized tissue<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=F, NS, Other combinations<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Knaub_LA&diff=161378
Knaub LA
2018-08-22T13:15:55Z
<p>Kandolf Georg: Redirected page to Knaub L</p>
<hr />
<div>#REDIRECT[[Knaub L]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Knaub_LA&diff=161377
Knaub LA
2018-08-22T13:15:42Z
<p>Kandolf Georg: Redirected page to Kaub L</p>
<hr />
<div>#REDIRECT[[Kaub L]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Nacarelli_2018_Geroscience&diff=161374
Nacarelli 2018 Geroscience
2018-08-22T12:51:24Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C (2018) Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts. Geroscience [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29931650 PMID: 29931650]<br />
|authors=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C<br />
|year=2018<br />
|journal=Geroscience<br />
|abstract=Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin. Measurements of mitochondrial function indicate that direct mitochondria targets of rapamycin are succinate dehydrogenase and matrix alanine aminotransferase. Elevated activity of these enzymes could be part of complex mechanisms that enable mitochondria to resume their optimal oxidative phosphorylation and resist senescence. This interpretation is supported by the fact that rapamycin-treated cultures do not undergo a premature senescence in response to the replacement of glucose with galactose in the culture medium, which forces a greater reliance on oxidative phosphorylation. Additionally, long-term treatment with rapamycin increases expression of the mitochondrial carrier protein UCP2, which facilitates the movement of metabolic intermediates across the mitochondrial membrane. The results suggest that rapamycin impacts mitochondrial function both through direct interaction with the mitochondria and through altered gene expression of mitochondrial carrier proteins.<br />
|keywords=Senescence, Cardiac fibroblasts, Oxidative phosphorylation, Alanine aminotransferase, Rapamycin, Aging<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=US PA Philadelphia Orynbayeva Z<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology<br />
|diseases=Aging;senescence<br />
|organism=Human<br />
|tissues=Heart, Fibroblast<br />
|preparations=Isolated mitochondria<br />
|couplingstates=OXPHOS<br />
|pathways=F, N, S, NS<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Nacarelli_2018_Geroscience&diff=161369
Nacarelli 2018 Geroscience
2018-08-22T11:49:29Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C (2018) Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts. Geroscience [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29931650 PMID: 29931650]<br />
|authors=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C<br />
|year=2018<br />
|journal=Geroscience<br />
|abstract=Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin. Measurements of mitochondrial function indicate that direct mitochondria targets of rapamycin are succinate dehydrogenase and matrix alanine aminotransferase. Elevated activity of these enzymes could be part of complex mechanisms that enable mitochondria to resume their optimal oxidative phosphorylation and resist senescence. This interpretation is supported by the fact that rapamycin-treated cultures do not undergo a premature senescence in response to the replacement of glucose with galactose in the culture medium, which forces a greater reliance on oxidative phosphorylation. Additionally, long-term treatment with rapamycin increases expression of the mitochondrial carrier protein UCP2, which facilitates the movement of metabolic intermediates across the mitochondrial membrane. The results suggest that rapamycin impacts mitochondrial function both through direct interaction with the mitochondria and through altered gene expression of mitochondrial carrier proteins.<br />
|keywords=Senescence, Cardiac fibroblasts, Oxidative phosphorylation, Alanine aminotransferase, Rapamycin, Aging<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=US PA Philadelphia Orynbayeva Z<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|diseases=Aging;senescence<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Geroscience&diff=161368
Geroscience
2018-08-22T11:47:56Z
<p>Kandolf Georg: Created page with "{{Journal |Title=[https://link.springer.com/journal/11357 Geroscience] }}"</p>
<hr />
<div>{{Journal<br />
|Title=[https://link.springer.com/journal/11357 Geroscience]<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Nacarelli_2018_Geroscience&diff=161367
Nacarelli 2018 Geroscience
2018-08-22T11:43:57Z
<p>Kandolf Georg: Created page with "{{Publication |title=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C (2018) Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac f..."</p>
<hr />
<div>{{Publication<br />
|title=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C (2018) Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts. Geroscience [Epub ahead of print].<br />
|info=[[https://www.ncbi.nlm.nih.gov/pubmed/29931650 PMID: 29931650]]<br />
|authors=Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C<br />
|year=2018<br />
|journal=Geroscience<br />
|abstract=Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin. Measurements of mitochondrial function indicate that direct mitochondria targets of rapamycin are succinate dehydrogenase and matrix alanine aminotransferase. Elevated activity of these enzymes could be part of complex mechanisms that enable mitochondria to resume their optimal oxidative phosphorylation and resist senescence. This interpretation is supported by the fact that rapamycin-treated cultures do not undergo a premature senescence in response to the replacement of glucose with galactose in the culture medium, which forces a greater reliance on oxidative phosphorylation. Additionally, long-term treatment with rapamycin increases expression of the mitochondrial carrier protein UCP2, which facilitates the movement of metabolic intermediates across the mitochondrial membrane. The results suggest that rapamycin impacts mitochondrial function both through direct interaction with the mitochondria and through altered gene expression of mitochondrial carrier proteins.<br />
|keywords=Senescence, Cardiac fibroblasts, Oxidative phosphorylation, Alanine aminotransferase, Rapamycin, Aging<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=US PA Philadelphia Orynbayeva Z<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|diseases=Aging;senescence<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Help:Person&diff=161317
Help:Person
2018-08-21T14:07:29Z
<p>Kandolf Georg: /* Add a person */</p>
<hr />
<div>__TOC__<br />
== Add a person ==<br />
<br />
* Format for person names in [[Form:Person]]<br />
* Format for author names in [[Form:Publication]]<br />
* Format for person name in [[Form:O2k-Network Lab]]<br />
* Profile pictures of persons should have a 3:4 ratio.<br />
<br />
:* Family name_Initials (no punctuation). The initials should be confirmed from publications, such that author names and person names are linked.<br />
:* Double first names: no spaces and no hyphens are used, e.g. Jean-Pierre Mazat is written as 'Mazat JP'.<br />
:* Double family names: Hyphenated double names (e.g. Aber-Nein) are written as 'Aber-Nein'; if double names are separated by a space (e.g. Aber Ja) use the space, 'Aber Ja'.<br />
:* '''Special letters (umlauts or accented letters) should be written as: ä=ae, ö=oe, ü=ue, é=e; â=a; æ=ae, å=aa, ø=oe.'''<br />
<br />
<br />
::: '''1. create Mueller Engelbert F'''<br />
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::::* Type “Mueller Engelbert F” into the search bar ->search<br />
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::::* Create the page “Mueller Engelbert F” on this wiki ->click<br />
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::::* Edit, type in <nowiki>"{{Person}}"</nowiki><br />
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::::* Edit with form, fill in person profile information<br />
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::: '''2. create Mueller EF'''<br />
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::::* MOVE “Mueller Engelbert F" to "Mueller EF"<br />
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:::: This puts the focus on the central profile page Mueller EF while all redirects are possible and do not interfere with the system.<br />
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::: '''Profiles with wrong redirects'''<br />
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:::: If you run across old redirects, i.e. Hauser Daniel as the main page and Hauser D with a redirect to Hauser Daniel, please correct them according to the following procedure:<br />
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::::* '''1. Hauser E: DELETE'''<br />
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::::* '''2. Hauser Daniel MOVE to Hauser E'''<br />
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== Address: Format for cities ==<br />
* Format for city name in [[Form:O2k-Network Lab]]<br />
:* English city names are preferred: e.g. München is written as 'Munich', Wien as 'Vienna'.<br />
:* No punctuation: e.g. 'St Petersburg'<br />
:* Double city names: Hyphenated double names (e.g. Aber-Nein) are written as 'Aber-Nein'; if double names are separated by a space (e.g. Rio de Janeiro) use the space, 'Rio de Janeiro'.<br />
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[[Category:Help]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Jelenik_2018_Mol_Metab&diff=161305
Jelenik 2018 Mol Metab
2018-08-21T13:41:56Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Jelenik T, Dille M, Müller-Lühlhoff S, Kabra DG, Zhou Z, Binsch C, Hartwig S, Lehr S, Chadt A, Peters EMJ, Kruse J, Roden M, Al-Hasani H, Castañeda TR (2018) FGF21 regulates insulin sensitivity following long-term chronic stress. Mol Metab [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29980484 PMID: 29980484 Open Access]<br />
|authors=Jelenik T, Dille M, Mueller-Luehlhoff S, Kabra DG, Zhou Z, Binsch C, Hartwig S, Lehr S, Chadt A, Peters EMJ, Kruse J, Roden M, Al-Hasani H, Castaneda TR<br />
|year=2018<br />
|journal=Mol Metab<br />
|abstract=Post-traumatic stress disorder (PTSD) increases type 2 diabetes risk, yet the underlying mechanisms are unclear. We investigated how early-life exposure to chronic stress affects long-term insulin sensitivity.<br />
<br />
C57Bl/6J mice were exposed to chronic variable stress for 15 days (Cvs) and then recovered for three months without stress (Cvs3m).<br />
<br />
Cvs mice showed markedly increased plasma corticosterone and hepatic insulin resistance. Cvs3m mice exhibited improved whole-body insulin sensitivity along with enhanced adipose glucose uptake and skeletal muscle mitochondrial function and fatty acid oxidation. Plasma ''FGF21'' levels were substantially increased and associated with expression of genes involved in fatty acid oxidation and formation of brown-like adipocytes. In humans, serum ''FGF21'' levels were associated with stress coping long time after the exposure.<br />
<br />
Early-life exposure to chronic stress leads to long term improvements in insulin sensitivity, oxidative metabolism and adipose tissue remodeling. ''FGF21'' contributes to a physiological memory mechanism to maintain metabolic homeostasis.<br />
<br />
<small>Copyright © 2018 The Authors. Published by Elsevier GmbH. All rights reserved.</small><br />
|keywords=Chronic variable stress, Diabetes, ''FGF21'', Insulin sensitivity, PTSD, White adipose tissue<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=DE Duesseldorf Roden M<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|diseases=Diabetes, Other<br />
|organism=Mouse<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized tissue<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=F, N, NS<br />
|instruments=Oxygraph-2k, O2k-Fluorometer<br />
|additional=Labels, 2018-08, Amplex UltraRed<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Casal_2018_J_Anim_Sci&diff=161269
Casal 2018 J Anim Sci
2018-08-21T12:25:55Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Casal A, Garcia-Roche M, Navajas EA, Cassina A, Carriquiry M (2018) Hepatic mitochondrial function in Hereford steers with divergent residual feed intake phenotypes. J Anim Sci [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30032298 PMID: 30032298]<br />
|authors=Casal A, Garcia-Roche M, Navajas EA, Cassina A, Carriquiry M<br />
|year=2018<br />
|journal=J Anim Sci<br />
|abstract=Variations in phenotypic expression of feed efficiency could be associated with differences or inefficiencies in mitochondria function due to its impact on energy expenditure. The aim of this study was to determine hepatic mitochondrial density and function in terms of respiration, gene and protein expression, and enzyme activity of mitochondrial respiratory complex proteins, in steers of divergent residual feed intake (RFI) phenotypes. Hereford steers (n = 111 and n = 122 for yr 1 and 2, respectively) were evaluated in post-weaning 70 d standard test for RFI. Forty-six steers exhibiting the greatest (n = 9 and 16 for yr 1 and 2; high-RFI) and the lowest (n = 9 and 12 for yr 1 and 2; low-RFI) RFI values were selected for this study. After the test, steers were managed together until slaughter under grazing conditions until they reached the slaughter body weight. At slaughter, hepatic samples (biopsies) were obtained. Tissue respiration was evaluated using high-resolution respirometry methods. Data were analyzed using a mixed model that included RFI group as fixed effect and slaughter date and year as a random effect using PROC MIXED of SAS. Residual feed intake and dry matter intake were different (P < 0.001) between low and high-RFI groups of yr 1, yr 2. Basal respiration and maximum respiratory rate were greater (P ≤ 0.04) for low than high-RFI steers when complex II substrates (succinate) were supplied. However, when Complex I substrates (glutamate/malate) were used maximum respiratory capacity tended to be greater (P < 0.09) for low vs. high-RFI steers. Low-RFI steers presented greater mitochondria density markers (greater (P < 0.05) citrate synthase (CS) activity and tended (P ≤ 0.08) to have greater CS mRNA and mtDNA:nDNA ratio) than high-RFI steers. Hepatic expression ''SDHA'', ''UQCRC1'' and ''CYC1'' mRNA was greater (P ≤ 0.02) and expression of ''NDUFA4'', ''NDUFA13'', ''SDHD'', ''UQCRH'' and ''ATP5E'' mRNA tended (P ≤ 0.10) to be greater in low than high-RFI steers. Hepatic ''SDHA'' protein expression tended (P < 0.08) to be greater while succinate dehydrogenase activity was greater (P = 0.04) and NADH dehydrogenase activity was greater (P = 0.03) for low than high-RFI steers. High-efficiency steers (low-RFI) probably had greater efficiency in hepatic nutrient metabolism, which was strongly associated with greater hepatic mitochondrial density and functioning, mainly of mitochondrial complex II.<br />
|keywords=Beef cattle, Feed efficiency, Liver, Mitochondria, Oxygen consumption<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=UY Montevideo Radi R<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, nDNA;cell genetics, Exercise physiology;nutrition;life style<br />
|organism=Bovines<br />
|tissues=Liver<br />
|preparations=Intact cells<br />
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=N, S, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Cassina_A&diff=161268
Cassina A
2018-08-21T12:25:39Z
<p>Kandolf Georg: Redirected page to Cassina AM</p>
<hr />
<div>#REDIRECT[[Cassina AM]]</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Paech_2018b_Toxicology&diff=161267
Paech 2018b Toxicology
2018-08-21T12:23:31Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krähenbühl S (2018) Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology 409:13-23.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30031043 PMID: 30031043]<br />
|authors=Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Kraehenbuehl S<br />
|year=2018<br />
|journal=Toxicology<br />
|abstract=Reports concerning hepatic mitochondrial toxicity of sunitinib are conflicting. We therefore decided to conduct a toxicological study in mice. After having determined the highest dose that did not affect nutrient ingestion and body weight, we treated mice orally with sunitinib (7.5 mg/kg/day) for 2 weeks. At the end of treatment, peak sunitinib plasma concentrations were comparable to those achieved in humans and liver concentrations were approximately 25-fold higher than in plasma. Sunitinib did not affect body weight, but increased plasma ALT activity 6-fold. The activity of enzyme complexes of the electron transport chain (ETC) was decreased numerically in freshly isolated and complex III activity significantly in previously frozen liver mitochondria. In previously frozen mitochondria, sunitinib decreased NADH oxidase activity concentration-dependently in both treatment groups. The hepatic mitochondrial reactive oxygen species (ROS) content and superoxide dismutase 2 expression were increased in sunitinib-treated mice. Protein and mRNA expression of several subunits of mitochondrial enzyme complexes were decreased in mitochondria from sunitinib-treated mice. Protein expression of PGC-1α, citrate synthase activity and mtDNA copy number were all decreased in livers of sunitinib-treated mice, indicating impaired mitochondrial proliferation. Caspase 3 activation and TUNEL-positive hepatocytes were increased in livers of sunitinib-treated mice, indicating hepatocyte apoptosis. In conclusion, sunitinib caused concentration-dependent toxicity in isolated mitochondria at concentrations reached in livers ''in vivo'' and inhibited hepatic mitochondrial proliferation. Daily mitochondrial insults and impaired mitochondrial proliferation most likely explain hepatocellular injury observed in mice treated with sunitinib.<br />
|keywords=Apoptosis, Hepatotoxicity, Mitochondrial toxicity, PGC-1α, Reactive oxygen species (ROS), Sunitinib<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=CH Basel Kraehenbuehl S<br />
}}<br />
{{Labeling<br />
|area=Respiration, mtDNA;mt-genetics, Pharmacology;toxicology<br />
|injuries=Cell death, Cryopreservation<br />
|organism=Mouse<br />
|tissues=Liver<br />
|preparations=Isolated mitochondria<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=N, S, DQ, CIV, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Paech_2018a_Toxicology&diff=161265
Paech 2018a Toxicology
2018-08-21T12:21:28Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Paech F, Mingard C, Grünig D, Abegg VF, Bouitbir J, Krähenbühl S (2018) Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib, regorafenib and sorafenib in human hepatic HepG2 cells. Toxicology 395:34-44.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29341879 PMID: 29341879]<br />
|authors=Paech F, Mingard C, Gruenig D, Abegg VF, Bouitbir J, Kraehenbuehl S<br />
|year=2018<br />
|journal=Toxicology<br />
|abstract=Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 h, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 h and in isolated mouse liver mitochondria exposed acutely. As a consequence, they increased mitochondrial production of ROS in HepG2 cells in a time- and concentration-dependent fashion and decreased the mitochondrial membrane potential concentration-dependently. In HepG2 cells exposed for 24 h, they induced mitochondrial fragmentation, lysosome content and mitophagy as well as mitochondrial release of cytochrome c, leading to apoptosis and/or necrosis. In conclusion, the kinase inhibitors ponatinib, regorafenib, and sorafenib impaired the function of the respiratory chain, which was associated with increased ROS production and a drop in the mitochondrial membrane potential. Despite activation of defense measures such as mitochondrial fission and mitophagy, some cells were liquidated concentration-dependently by apoptosis or necrosis. Mitochondrial dysfunction may represent a toxicological mechanism of hepatotoxicity associated with certain kinase inhibitors.<br />
|keywords=Apoptosis, Hepatotoxicity, Kinase inhibitor, Mitochondrial fission & mitophagy, Mitochondrial toxicity, Reactive oxygen species (ROS)<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=CH Basel Kraehenbuehl S<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Medicine<br />
|diseases=Cancer<br />
|organism=Human, Mouse<br />
|tissues=Liver, Other cell lines<br />
|preparations=Permeabilized cells, Isolated mitochondria<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=N, S, DQ, CIV, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-03<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Paech_2018b_Toxicology&diff=161264
Paech 2018b Toxicology
2018-08-21T12:19:43Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Krähenbühl S (2018) Sunitinib induces hepatocyte mitochondrial damage and apoptosis in mice. Toxicology 409:13-23.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30031043 PMID: 30031043]<br />
|authors=Paech F, Abegg VF, Duthaler U, Terracciano L, Bouitbir J, Kraehenbuehl S<br />
|year=2018<br />
|journal=Toxicology<br />
|abstract=Reports concerning hepatic mitochondrial toxicity of sunitinib are conflicting. We therefore decided to conduct a toxicological study in mice. After having determined the highest dose that did not affect nutrient ingestion and body weight, we treated mice orally with sunitinib (7.5 mg/kg/day) for 2 weeks. At the end of treatment, peak sunitinib plasma concentrations were comparable to those achieved in humans and liver concentrations were approximately 25-fold higher than in plasma. Sunitinib did not affect body weight, but increased plasma ALT activity 6-fold. The activity of enzyme complexes of the electron transport chain (ETC) was decreased numerically in freshly isolated and complex III activity significantly in previously frozen liver mitochondria. In previously frozen mitochondria, sunitinib decreased NADH oxidase activity concentration-dependently in both treatment groups. The hepatic mitochondrial reactive oxygen species (ROS) content and superoxide dismutase 2 expression were increased in sunitinib-treated mice. Protein and mRNA expression of several subunits of mitochondrial enzyme complexes were decreased in mitochondria from sunitinib-treated mice. Protein expression of PGC-1α, citrate synthase activity and mtDNA copy number were all decreased in livers of sunitinib-treated mice, indicating impaired mitochondrial proliferation. Caspase 3 activation and TUNEL-positive hepatocytes were increased in livers of sunitinib-treated mice, indicating hepatocyte apoptosis. In conclusion, sunitinib caused concentration-dependent toxicity in isolated mitochondria at concentrations reached in livers ''in vivo'' and inhibited hepatic mitochondrial proliferation. Daily mitochondrial insults and impaired mitochondrial proliferation most likely explain hepatocellular injury observed in mice treated with sunitinib.<br />
|keywords=Apoptosis, Hepatotoxicity, Mitochondrial toxicity, PGC-1α, Reactive oxygen species (ROS), Sunitinib<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=CH Basel Kraehenbuehl S<br />
}}<br />
{{Labeling<br />
|area=Respiration, mtDNA;mt-genetics, Pharmacology;toxicology<br />
|injuries=Cell death, Cryopreservation<br />
|organism=Mouse<br />
|tissues=Liver<br />
|preparations=Isolated mitochondria<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=N, S, DQ, CIV, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Sci_Rep&diff=161241
Sci Rep
2018-08-20T13:09:32Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Journal<br />
|Title=[https://www.journals.elsevier.com/international-journal-of-cardiology International Journal of Cardiology]<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Hafen_2018_J_Appl_Physiol_(1985)&diff=161240
Hafen 2018 J Appl Physiol (1985)
2018-08-20T13:07:46Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Hafen PS, Preece CN, Sorensen JR, Hancock CR, Hyldahl RD (2018) Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle. J Appl Physiol (1985) [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30024339 PMID: 30024339]<br />
|authors=Hafen PS, Preece CN, Sorensen JR, Hancock CR, Hyldahl RD<br />
|year=2018<br />
|journal=J Appl Physiol (1985)<br />
|abstract=The heat stress response is associated with several beneficial adaptations that promote cell health and survival. Specifically, ''in vitro'' and animal investigations suggest that repeated exposures to a mild heat stress (~40°C) elicits positive mitochondrial adaptations in skeletal muscle comparable to those observed with exercise. To assess whether such adaptations translate to human skeletal muscle, we produced local, deep tissue heating of the ''vastus lateralis'' via pulsed shortwave diathermy in 20 men (n=10) and women (n=10). Diathermy increased muscle temperature by 3.9 °C within 30 minutes of application. Immediately following a single 2-hr heating session, we observed increased phosphorylation of AMPK and ERK1/2, but not of p38 MAPK nor JNK. Following repeated heat exposures (2-hr daily for 6 consecutive days), we observed a significant cellular heat stress response, as heat shock protein 70 and 90 increased 45% and 38%, respectively. In addition, PGC-1α and mitochondrial electron transport protein complexes I and V expression were increased after heating. These increases were accompanied by augmentation of maximal coupled, and uncoupled, respiratory capacity, measured via high-resolution respirometry. Our data provide the first evidence that mitochondrial adaptation can be elicited in human skeletal muscle in response to repeated exposures to mild heat stress.<br />
|keywords=Heat Stress, Mitochondrial adaptation, Human skeletal muscle<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=US UT Provo Hancock CR<br />
}}<br />
{{Labeling<br />
|area=Respiration, Comparative MiP;environmental MiP<br />
|injuries=Temperature<br />
|organism=Human<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized tissue<br />
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase<br />
|couplingstates=OXPHOS, ET<br />
|pathways=N, S, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Hafen_2018_J_Appl_Physiol_(1985)&diff=161237
Hafen 2018 J Appl Physiol (1985)
2018-08-20T12:43:16Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Hafen PS, Preece CN, Sorensen JR, Hancock CR, Hyldahl RD (2018) Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle. J Appl Physiol (1985) [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30024339 PMID: 30024339]<br />
|authors=Hafen PS, Preece CN, Sorensen JR, Hancock CR, Hyldahl RD<br />
|year=2018<br />
|journal=J Appl Physiol (1985)<br />
|abstract=The heat stress response is associated with several beneficial adaptations that promote cell health and survival. Specifically, ''in vitro'' and animal investigations suggest that repeated exposures to a mild heat stress (~40°C) elicits positive mitochondrial adaptations in skeletal muscle comparable to those observed with exercise. To assess whether such adaptations translate to human skeletal muscle, we produced local, deep tissue heating of the ''vastus lateralis'' via pulsed shortwave diathermy in 20 men (n=10) and women (n=10). Diathermy increased muscle temperature by 3.9 °C within 30 minutes of application. Immediately following a single 2-hr heating session, we observed increased phosphorylation of AMPK and ERK1/2, but not of p38 MAPK nor JNK. Following repeated heat exposures (2-hr daily for 6 consecutive days), we observed a significant cellular heat stress response, as heat shock protein 70 and 90 increased 45% and 38%, respectively. In addition, PGC-1α and mitochondrial electron transport protein complexes I and V expression were increased after heating. These increases were accompanied by augmentation of maximal coupled, and uncoupled, respiratory capacity, measured via high-resolution respirometry. Our data provide the first evidence that mitochondrial adaptation can be elicited in human skeletal muscle in response to repeated exposures to mild heat stress.<br />
|keywords=Heat Stress, Mitochondrial adaptation, Human skeletal muscle<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=US UT Provo Hancock CR<br />
}}<br />
{{Labeling<br />
|area=Respiration, Comparative MiP;environmental MiP<br />
|injuries=Temperature<br />
|organism=Human<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized cells<br />
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase<br />
|couplingstates=OXPHOS, ET<br />
|pathways=N, S, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Acta_Diabetol&diff=161236
Acta Diabetol
2018-08-20T12:23:49Z
<p>Kandolf Georg: Created page with "{{Journal |Title=[https://link.springer.com/journal/592 Acta Diabetologica] }}"</p>
<hr />
<div>{{Journal<br />
|Title=[https://link.springer.com/journal/592 Acta Diabetologica]<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Barca_2018_Hum_Mol_Genet&diff=161217
Barca 2018 Hum Mol Genet
2018-08-20T09:50:56Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick E, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ (2018) USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Hum Mol Genet [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29917077 PMID: 29917077 Open Access]<br />
|authors=Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick E, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ<br />
|year=2018<br />
|journal=Hum Mol Genet<br />
|abstract=Leigh syndrome is a frequent, heterogeneous pediatric presentation of mitochondrial oxidative phosphorylation (OXPHOS) disease, manifesting with psychomotor retardation and necrotizing lesions in brain deep gray matter. OXPHOS occurs at the inner mitochondrial membrane through the integrated activity of 5 protein complexes, of which complex V (CV) functions in a dimeric form to directly generate adenosine triphosphate (ATP). Mutations in several different structural CV subunits cause Leigh syndrome; however, dimerization defects have not been associated with human disease. We report four Leigh syndrome subjects from three unrelated Ashkenazi-Jewish families harboring a homozygous splice-site mutation (c.87 + 1G>C) in a novel CV subunit disease gene, ''USMG5''. The Ashkenazi population allele frequency is 0.57%. This mutation produces two ''USMG5'' transcripts, wild-type and lacking exon 3. Fibroblasts from two Leigh syndrome probands had reduced wild-type ''USMG5'' mRNA expression and undetectable protein. The mutation did not alter monomeric CV expression, but reduced both CV dimer expression and ATP synthesis rate. Rescue with wild-type ''USMG5'' cDNA in proband fibroblasts restored USMG5 protein, increased CV dimerization and enhanced ATP production rate. These data demonstrate that a recurrent ''USMG5'' splice-site founder mutation in the Ashkenazi Jewish population causes autosomal recessive Leigh syndrome by reduction of CV dimerization and ATP synthesis.<br />
|keywords=Leigh syndrome, Mitochondrial diseases, Complex V, ATP synthase, Encephalopathy<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=US PA Philadelphia Wallace DC, US PA Philadelphia Falk MJ<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Structure;fission;fusion, nDNA;cell genetics<br />
|diseases=Neurodegenerative, Other<br />
|organism=Human<br />
|tissues=Fibroblast<br />
|preparations=Intact cells, Permeabilized cells<br />
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase<br />
|topics=Coupling efficiency;uncoupling<br />
|couplingstates=LEAK, ROUTINE, OXPHOS, ET<br />
|pathways=F, N, S, DQ, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Barca_2018_Hum_Mol_Genet&diff=161216
Barca 2018 Hum Mol Genet
2018-08-20T09:48:40Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Publication<br />
|title=Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick E, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ (2018) USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Hum Mol Genet [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29917077 PMID: 29917077 Open Access]<br />
|authors=Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick E, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ<br />
|year=2018<br />
|journal=Hum Mol Genet<br />
|abstract=Leigh syndrome is a frequent, heterogeneous pediatric presentation of mitochondrial oxidative phosphorylation (OXPHOS) disease, manifesting with psychomotor retardation and necrotizing lesions in brain deep gray matter. OXPHOS occurs at the inner mitochondrial membrane through the integrated activity of 5 protein complexes, of which complex V (CV) functions in a dimeric form to directly generate adenosine triphosphate (ATP). Mutations in several different structural CV subunits cause Leigh syndrome; however, dimerization defects have not been associated with human disease. We report four Leigh syndrome subjects from three unrelated Ashkenazi-Jewish families harboring a homozygous splice-site mutation (c.87 + 1G>C) in a novel CV subunit disease gene, USMG5. The Ashkenazi population allele frequency is 0.57%. This mutation produces two USMG5 transcripts, wild-type and lacking exon 3. Fibroblasts from two Leigh syndrome probands had reduced wild-type USMG5 mRNA expression and undetectable protein. The mutation did not alter monomeric CV expression, but reduced both CV dimer expression and ATP synthesis rate. Rescue with wild-type USMG5 cDNA in proband fibroblasts restored USMG5 protein, increased CV dimerization and enhanced ATP production rate. These data demonstrate that a recurrent USMG5 splice-site founder mutation in the Ashkenazi Jewish population causes autosomal recessive Leigh syndrome by reduction of CV dimerization and ATP synthesis.<br />
|keywords=Leigh syndrome, Mitochondrial diseases, Complex V, ATP synthase, Encephalopathy<br />
|editor=[[Plangger M]], [[Kandolf G]],<br />
|mipnetlab=US PA Philadelphia Wallace DC, US PA Philadelphia Falk MJ<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Structure;fission;fusion, nDNA;cell genetics<br />
|diseases=Other<br />
|organism=Human<br />
|tissues=Fibroblast<br />
|preparations=Intact cells, Permeabilized cells<br />
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase<br />
|topics=Coupling efficiency;uncoupling<br />
|couplingstates=LEAK, ROUTINE, OXPHOS, ET<br />
|pathways=F, N, S, DQ, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08,<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Chakrabarti_2018_MiP2018&diff=161215
Chakrabarti 2018 MiP2018
2018-08-20T09:47:16Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=[[Image:MiPsocietyLOGO.JPG|left|90px|Mitochondrial Physiology Society|MiPsociety]] ''Fatty acid binding protein 3'' regulation of mitochondrial lipids - A strategy for exceptional longevity in the ''Pipistrelle'' bat.<br />
|info=[[MiP2018]]<br />
|authors=Pollard AK, Ingram TL, Ortori CA, Shephard F, Liddell S, Barrett DA, Chakrabarti L<br />
|year=2018<br />
|event=MiP2018<br />
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]<br />
It is generally accepted that smaller mammals with higher metabolic rates have shorter maximal lifespans. The very few mammalian species that don’t abide by these rules can give insight into how the detrimental effects of ageing may be delayed. The recorded maximum lifespans of micro-bats are exceptional, reaching over 40 years, compared with the similarly-sized laboratory mouse of 4 years. We investigated the possibility that differences in the biochemical composition of mitochondria might be associated with maximal life-span differences between bat and mouse species. We used 2D gel electrophoresis for proteomics and ultra-high performance liquid chromatography coupled with high resolution mass spectrometry lipidomics, to interrogate mitochondrial fractions prepared from ''Mus musculus'' and ''Pipistrelle pipistrellus'' brain and skeletal muscle. Identified potential modifiers of mitochondrial ageing were further investigated in ''Caenorhabditis elegans'' RNAi knock-downs for lipid binding proteins 4, 5 and 6. We show that mitochondrial proteomes are distinctly different when comparing mouse with bat, and their mitochondrial lipid signatures clearly define the tissue and species of origin. In the bat high levels of free fatty acids and N-acylethanolamine lipid species together with a significantly greater abundance of fatty acid binding protein 3 in muscle (1.8 fold, p=0.037) comprise a pathway which may be important for increased longevity in mammals. Manipulation of fatty acid binding protein orthologues in ''C.elegans'' confirmed these proteins connect mitochondrial function and lifespan. Our comparison is the first to delineate mitochondrial profiles in the bat to reveal an intrinsic biochemistry consistent with an enhanced ability to counter detrimental effects of ageing[1–4].<br />
|editor=[[Plangger M]], [[Kandolf G]]<br />
}}<br />
{{Labeling<br />
|area=mt-Membrane, Comparative MiP;environmental MiP<br />
|diseases=Aging;senescence<br />
|organism=Mouse, Other mammals, Caenorhabditis elegans<br />
|tissues=Skeletal muscle, Nervous system<br />
|topics=Fatty acid<br />
}}<br />
== Affiliations ==<br />
Pollard AK(1), Ingram TL(1), Ortori CA(3), Shephard F(1), Liddell S(2), Barrett DA(3), Chakrabarti L(1,4)<br />
::::#School Veterinary Medicine Science<br />
::::#School Biosciences<br />
::::#Centre Analytical Bioscience, School Pharmacy; Univ Nottingham, Sutton Bonington, UK<br />
::::#MRC-ARUK Centre Musculoskeletal Ageing. - lisa.chakrabarti@nottingham.ac.uk<br />
<br />
== Figures ==<br />
[[File:Chakrabarti_Figure_MiP2018.jpg|left|400 px]] Figure 1. '''Mitochondrial lipid composition differs between the bat and mouse mitochondrial proteomes.''' Orthogonal partial least square-discriminant analysis (OPLS-DA) of lipids found in the brain and skeletal muscle mitochondria from the mouse and the bat. Separation across the x-axis is according to tissue type with the skeletal muscle mitochondrial samples congregating to the left quadrants and the brain mitochondrial samples to the right. Along the y-axis separation delineates mammalian species with the bat mitochondrial samples grouping at the lower quadrants and the mouse mitochondrial samples grouping at the upper quadrants. Bat brain (BB) mitochondrial samples (adult, n=10) are shown on the OPLS-DA by the green circles. Bat skeletal muscle (BM) mitochondria (adult, n=10) are indicated by the dark blue circles. Young mouse brain (YMB) mitochondria aged 4-11 weeks (n=10) and aged mouse brain mitochondria (OMB) aged 78 weeks (n=10) are denoted by orange and red circles respectively. Young mouse skeletal (YMM) muscle mitochondria aged 4-11 weeks (n=9) and aged mouse skeletal muscle mitochondria (OMM) aged 78 weeks (n=10) are indicated by the yellow and blue circles, respectively. <br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
== References ==<br />
::::#Pollard A, Shephard F, Freed J, Liddell S, Chakrabarti L (2016) Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. Aging (Albany NY) 8:2425-36.<br />
::::#Pollard AK, Ortori CA, Stöger R, Barrett DA, Chakrabarti L (2017) Mouse mitochondrial lipid composition is defined by age in brain and muscle. Aging (Albany NY) 9:986-98.<br />
::::#Ingram T, Chakrabarti L (2016) Proteomic profiling of mitochondria: what does it tell us about the ageing brain? Aging (Albany NY) 8:3161-79.<br />
::::#Foley NM, Hughes GM, Huang Z, Clarke M, Jebb D, Whelan CV, Petit EJ, Touzalin F, Farcy O, Jones G, Ransome RD, Kacprzyk J, O'Connell MJ, Kerth G, Rebelo H, Rodrigues L, Puechmaille SJ, Teeling EC (2018) Growing old, yet staying young: The role of telomeres in bats’ exceptional longevity. Sci Adv 4:eaao0926.</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=McCurdy_2018_Endocrine_Reviews&diff=161212
McCurdy 2018 Endocrine Reviews
2018-08-20T08:40:51Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=McCurdy CE, True C, Takahashi D, Hetrick B, Varlamov O, Roberts CT (2018) Chronic hyperandrogenemia impairs oxidative metabolism in skeletal muscle from adolescent female rhesus macaques. Endocrine Reviews.<br />
|info=[https://www.endocrine.org/meetings/endo-annual-meetings/abstract-details?ID=24972]<br />
|authors=McCurdy CE, True C, Takahashi D, Hetrick B, Varlamov O, Roberts CT<br />
|year=2018<br />
|event=Endocrine Reviews<br />
|abstract=Polycystic ovary syndrome is associated with skeletal muscle insulin resistance and an increased risk for developing type 2 diabetes, independent of obesity. The cellular mechanisms underlying skeletal muscle IR with elevated androgens in females is unknown. Considering that reduced metabolic flexibility and decreased mitochondrial oxidative phosphorylation are strongly linked to impaired muscle insulin sensitivity, the goal of this study was to examine the effects of chronically elevated androgen, with and without exposure to a western-style diet (WSD), on muscle fatty acid and carbohydrate oxidative metabolism in adolescent female rhesus macaques. We hypothesized that androgen treatment would impair substrate metabolism, and that concurrent consumption of a WSD would exacerbate defects in oxidative phosphorylation (OxPhos). Female rhesus macaques (2.5 yrs of age) were pair-housed and assigned to either a control diet (CON) or a WSD with 14% or 36% of calories derived from fat, respectively, for 2 years. Within each diet group, females received either a cholesterol implant (+C) or testosterone (+T) implant (serum T, 1-1.5 ng/mL) for the duration of the study. Overall, females in WSD+T group had the largest gains in body fat and were the most insulin-resistant (see related co-authored abstract). Carbohydrate and fatty acid oxidation were measured by high-resolution respirometry in separate protocols in permeabilized muscle fiber bundles isolated from the gastrocnemius (n=6-9/group). Data were analyzed by a 2-way ANOVA (diet x T) with Tukey posthoc analysis. In the fatty acid protocol, there was a significant interaction between diet and testosterone exposure (P<0.005); WSD exposure resulted in a ~50% reduction in octanoylcarnitine oxidation, OxPhos capacity and maximal uncoupled electron transport system (ETS) capacity in the WSD+C group compared to CON+C group. In contrast, respiratory flux during the fatty acid protocol was not decreased in the WSD+T group, indicating that T prevented the changes induced by WSD. This prevention may be partially explained by T increasing OxPhos coupling efficiency and reducing leak capacity (P=0.02). In the carbohydrate protocol, there was also a significant interaction (P<0.005) such that in CON+T group, but not the WSD+T group, pyruvate oxidation, CI-linked OxPhos capacity, and maximal uncoupled ETS capacity were reduced by ~30-35% compared to the CON+C group. Mitochondrial number measured by citrate synthase activity was not different between groups. Overall, chronic exposure to WSD or T alone leads to a substrate-specific down-regulation of muscle oxidative metabolism in adolescent females. Combined exposure to WSD and T blocks the individual effects of WSD or T alone on fatty acid and carbohydrate metabolism, suggesting that each treatment may impinge on a common regulatory pathway.<br />
|editor=[[Kandolf G]],<br />
|mipnetlab=US OR Eugene McCurdy CE<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|diseases=Diabetes<br />
|organism=Other mammals<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized tissue<br />
|couplingstates=ET<br />
|pathways=F<br />
|instruments=Oxygraph-2k<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=McCurdy_2018_Endocrine_Reviews&diff=161211
McCurdy 2018 Endocrine Reviews
2018-08-20T08:40:36Z
<p>Kandolf Georg: Created page with "{{Abstract |title=McCurdy CE, True C, Takahashi D, Hetrick B, Varlamov O, Roberts CT (2018) Chronic hyperandrogenemia impairs oxidative metabolism in skeletal muscle from adol..."</p>
<hr />
<div>{{Abstract<br />
|title=McCurdy CE, True C, Takahashi D, Hetrick B, Varlamov O, Roberts CT (2018) Chronic hyperandrogenemia impairs oxidative metabolism in skeletal muscle from adolescent female rhesus macaques. Endocrine Reviews.<br />
|info=[https://www.endocrine.org/meetings/endo-annual-meetings/abstract-details?ID=24972]<br />
|authors=McCurdy CE, True C, Takahashi D, Hetrick B, Varlamov O, Roberts CT<br />
|year=2018<br />
|event=Endocrine Reviews<br />
|abstract=Polycystic ovary syndrome is associated with skeletal muscle insulin resistance and an increased risk for developing type 2 diabetes, independent of obesity. The cellular mechanisms underlying skeletal muscle IR with elevated androgens in females is unknown. Considering that reduced metabolic flexibility and decreased mitochondrial oxidative phosphorylation are strongly linked to impaired muscle insulin sensitivity, the goal of this study was to examine the effects of chronically elevated androgen, with and without exposure to a western-style diet (WSD), on muscle fatty acid and carbohydrate oxidative metabolism in adolescent female rhesus macaques. We hypothesized that androgen treatment would impair substrate metabolism, and that concurrent consumption of a WSD would exacerbate defects in oxidative phosphorylation (OxPhos). Female rhesus macaques (2.5 yrs of age) were pair-housed and assigned to either a control diet (CON) or a WSD with 14% or 36% of calories derived from fat, respectively, for 2 years. Within each diet group, females received either a cholesterol implant (+C) or testosterone (+T) implant (serum T, 1-1.5 ng/mL) for the duration of the study. Overall, females in WSD+T group had the largest gains in body fat and were the most insulin-resistant (see related co-authored abstract). Carbohydrate and fatty acid oxidation were measured by high-resolution respirometry in separate protocols in permeabilized muscle fiber bundles isolated from the gastrocnemius (n=6-9/group). Data were analyzed by a 2-way ANOVA (diet x T) with Tukey posthoc analysis. In the fatty acid protocol, there was a significant interaction between diet and testosterone exposure (P<0.005); WSD exposure resulted in a ~50% reduction in octanoylcarnitine oxidation, OxPhos capacity and maximal uncoupled electron transport system (ETS) capacity in the WSD+C group compared to CON+C group. In contrast, respiratory flux during the fatty acid protocol was not decreased in the WSD+T group, indicating that T prevented the changes induced by WSD. This prevention may be partially explained by T increasing OxPhos coupling efficiency and reducing leak capacity (P=0.02). In the carbohydrate protocol, there was also a significant interaction (P<0.005) such that in CON+T group, but not the WSD+T group, pyruvate oxidation, CI-linked OxPhos capacity, and maximal uncoupled ETS capacity were reduced by ~30-35% compared to the CON+C group. Mitochondrial number measured by citrate synthase activity was not different between groups. Overall, chronic exposure to WSD or T alone leads to a substrate-specific down-regulation of muscle oxidative metabolism in adolescent females. Combined exposure to WSD and T blocks the individual effects of WSD or T alone on fatty acid and carbohydrate metabolism, suggesting that each treatment may impinge on a common regulatory pathway.<br />
|editor=[[Kandolf G]],<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|diseases=Diabetes<br />
|organism=Other mammals<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized tissue<br />
|couplingstates=ET<br />
|pathways=F<br />
|instruments=Oxygraph-2k<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Greyslak_2018_FASEB_J&diff=161204
Greyslak 2018 FASEB J
2018-08-20T08:23:47Z
<p>Kandolf Georg: </p>
<hr />
<div>{{Abstract<br />
|title=Greyslak KT, Hetrick B, Takahashi DL, Dean T, Kievit P, Sullivan EL, McCurdy CE (2018) Exposure to a western-style diet during early development reduces skeletal muscle lipid metabolism and CI-dependent oxidative capacity in juvenile non-human primate offspring. FASEB J.<br />
|info=[https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1_supplement.lb398]<br />
|authors=Greyslak KT, Hetrick B, Takahashi DL, Dean T, Kievit P, Sullivan EL, McCurdy CE<br />
|year=2018<br />
|event=FASEB J<br />
|abstract=Maternal obesity and diabetes during pregnancy is linked to an increased and earlier risk for offspring to develop insulin resistance and metabolic diseases. We have previously found in a non-human primate model that maternal western-style diet (WSD) alone or in combination with obesity reduces oxidative capacity in fetal muscle concomitant with increased oxidative damage and lipid metabolism. The purpose of this study was to determine whether fetal adaptations to maternal WSD alone independent of maternal obesity leads to persistent reductions in skeletal muscle metabolism in juvenile offspring prior to the development of obesity.<br />
<br />
Lean adult female Japanese macaques were maintained on a control diet (CTR) or WSD prior to and during pregnancy and lactation. Male and female offspring were than weaned to independent housing at 7 mo and fed a WSD or CTR resulting in four groups (CTR/CTR, CTR/WSD, WSD/CTR and WSD/WSD). Insulin sensitivity was measured by i.v. GTT and body composition by DEXA at 36 mo. Muscle biopsies were taken at 40 mo to measure oxidative metabolism by high resolution respirometry and electron transport system complex (C) activities by spectrophotometry. Data were analyzed by a 2-way ANOVA (maternal diet X offspring diet)<br />
<br />
There were no differences in body weight, % fat or insulin sensitivity across groups. Total oxidative capacity and CI-dependent oxidative capacity were decreased by ~30% (P=0.001) in the presence of lipid substrates in gastrocnemius (gastroc) and soleus of offspring exposed to a maternal WSD independent of offspring diet. CI-specific activity was reduced by 50% (P<0.0001) in the gastroc. Citrate synthase activity was not different suggesting that reduced oxidative metabolism is not caused by diminished mitochondrial abundance.<br />
<br />
Maternal WSD during pregnancy and lactation results in a persistent reduction in skeletal muscle lipid metabolism in offspring prior to offspring obesity. Switching offspring to a heathy diet did not ameliorate the effects of developmental exposure to maternal WSD. Impaired muscle lipid metabolism is linked to insulin resistance in adults and likely contributes to the increased risk of metabolic disease in exposed offspring.<br />
<br />
Support or Funding Information:<br />
<br />
R24 DK090964R01 MH107508R01 (ES)<br />
|editor=[[Kandolf G]],<br />
|mipnetlab=US OR Eugene McCurdy CE<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|diseases=Obesity<br />
|organism=Other mammals<br />
|tissues=Skeletal muscle<br />
|pathways=N<br />
|instruments=Oxygraph-2k<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Greyslak_2018_FASEB_J&diff=161203
Greyslak 2018 FASEB J
2018-08-20T08:23:32Z
<p>Kandolf Georg: Created page with "{{Abstract |title=Greyslak KT, Hetrick B, Takahashi DL, Dean T, Kievit P, Sullivan EL, McCurdy CE (2018) Exposure to a western-style diet during early development reduces skel..."</p>
<hr />
<div>{{Abstract<br />
|title=Greyslak KT, Hetrick B, Takahashi DL, Dean T, Kievit P, Sullivan EL, McCurdy CE (2018) Exposure to a western-style diet during early development reduces skeletal muscle lipid metabolism and CI-dependent oxidative capacity in juvenile non-human primate offspring. FASEB J.<br />
|info=[https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1_supplement.lb398]<br />
|authors=Greyslak KT, Hetrick B, Takahashi DL, Dean T, Kievit P, Sullivan EL, McCurdy CE<br />
|year=2018<br />
|event=FASEB J<br />
|abstract=Maternal obesity and diabetes during pregnancy is linked to an increased and earlier risk for offspring to develop insulin resistance and metabolic diseases. We have previously found in a non-human primate model that maternal western-style diet (WSD) alone or in combination with obesity reduces oxidative capacity in fetal muscle concomitant with increased oxidative damage and lipid metabolism. The purpose of this study was to determine whether fetal adaptations to maternal WSD alone independent of maternal obesity leads to persistent reductions in skeletal muscle metabolism in juvenile offspring prior to the development of obesity.<br />
<br />
Lean adult female Japanese macaques were maintained on a control diet (CTR) or WSD prior to and during pregnancy and lactation. Male and female offspring were than weaned to independent housing at 7 mo and fed a WSD or CTR resulting in four groups (CTR/CTR, CTR/WSD, WSD/CTR and WSD/WSD). Insulin sensitivity was measured by i.v. GTT and body composition by DEXA at 36 mo. Muscle biopsies were taken at 40 mo to measure oxidative metabolism by high resolution respirometry and electron transport system complex (C) activities by spectrophotometry. Data were analyzed by a 2-way ANOVA (maternal diet X offspring diet)<br />
<br />
There were no differences in body weight, % fat or insulin sensitivity across groups. Total oxidative capacity and CI-dependent oxidative capacity were decreased by ~30% (P=0.001) in the presence of lipid substrates in gastrocnemius (gastroc) and soleus of offspring exposed to a maternal WSD independent of offspring diet. CI-specific activity was reduced by 50% (P<0.0001) in the gastroc. Citrate synthase activity was not different suggesting that reduced oxidative metabolism is not caused by diminished mitochondrial abundance.<br />
<br />
Maternal WSD during pregnancy and lactation results in a persistent reduction in skeletal muscle lipid metabolism in offspring prior to offspring obesity. Switching offspring to a heathy diet did not ameliorate the effects of developmental exposure to maternal WSD. Impaired muscle lipid metabolism is linked to insulin resistance in adults and likely contributes to the increased risk of metabolic disease in exposed offspring.<br />
<br />
Support or Funding Information:<br />
<br />
R24 DK090964R01 MH107508R01 (ES)<br />
|editor=[[Kandolf G]],<br />
}}<br />
{{Labeling<br />
|area=Respiration, Exercise physiology;nutrition;life style<br />
|diseases=Obesity<br />
|organism=Other mammals<br />
|tissues=Skeletal muscle<br />
|pathways=N<br />
|instruments=Oxygraph-2k<br />
}}</div>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Gao_2018_Free_Radic_Biol_Med&diff=161130
Gao 2018 Free Radic Biol Med
2018-08-20T06:41:24Z
<p>Kandolf Georg: Created page with "{{Publication |title=Gao JL, Zhao J, Zhu HB, Peng X, Zhu JX, Ma MH, Fu Y, Hu N, Tai Y, Xuan XC, Dong DL (2018) Characterizations of mitochondrial uncoupling induced by chemica..."</p>
<hr />
<div>{{Publication<br />
|title=Gao JL, Zhao J, Zhu HB, Peng X, Zhu JX, Ma MH, Fu Y, Hu N, Tai Y, Xuan XC, Dong DL (2018) Characterizations of mitochondrial uncoupling induced by chemical mitochondrial uncouplers in cardiomyocytes. Free Radic Biol Med 124:288-98.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29935261 PMID: 29935261]<br />
|authors=Gao JL, Zhao J, Zhu HB, Peng X, Zhu JX, Ma MH, Fu Y, Hu N, Tai Y, Xuan XC, Dong DL<br />
|year=2018<br />
|journal=Free Radic Biol Med<br />
|abstract=Induction of mild mitochondrial uncoupling is protective in a variety of disorders; however, it is unclear how to recognize the mild mitochondrial uncoupling induced by chemical mitochondrial uncouplers. The aim of the present study is to identify the pharmacological properties of mitochondrial uncoupling induced by mitochondrial uncouplers in cardiomyocytes. Neonatal rat cardiomyocytes were cultured. Protein levels were measured by using western blot technique. The whole cell respiratory function was determined by using high-resolution respirometry. The typical types of chemical mitochondrial uncouplers, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), niclosamide, and BAM15, induced biphasic change of STAT3 activity in cardiomyocytes, activating STAT3 at low dose and inhibiting STAT3 at high dose, though the dose range of these drugs was distinct. Low-dose uncouplers induced STAT3 activation through the mild increase of mitochondrial ROS (mitoROS) generation and the subsequent JAK/STAT3 activation in cardiomyocytes. However, high-dose uncouplers induced inhibition of STAT3, decrease of ATP production, and cardiomyocyte death. High-dose uncouplers induced STAT3 inhibition through the excessive mitoROS generation and the decreased ATP -induced AMPK activation. Low-dose mitochondrial uncouplers attenuated doxorubicin (DOX)-induced STAT3 inhibition and cardiomyocyte death, and activated STAT3 contributed to the cardioprotection of low-dose mitochondrial uncouplers. Uncoupler-induced mild mitochondrial uncoupling in cardiomyocytes is characterized by STAT3 activation and ATP increase whereas excessive mitochondrial uncoupling is characterized by STAT3 inhibition, ATP decrease and cell injury. Development of mitochondrial uncoupler with optimal dose window of inducing mild uncoupling is a promising strategy for heart protection.<br />
|keywords=Cardiomyocytes, MitoROS, Mitochondrial uncoupler, Mitochondrial uncoupling, STAT3<br />
|editor=[[Kandolf G]],<br />
|mipnetlab=CN Harbin Dong D<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|organism=Rat<br />
|tissues=Heart<br />
|preparations=Intact cells<br />
|topics=Uncoupler<br />
|couplingstates=LEAK, ROUTINE, ET<br />
|pathways=ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-08<br />
}}</div>
Kandolf Georg