Difference between revisions of "O2k-Publications: Topics"
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{{Publication}} | {{Publication | ||
{{Labeling}} | |title=Koizumi T, Watanabe M, Yokota T, Tsuda M, Handa H, Koya J, Nishino K, Tatsuta D, Natsui H, Kadosaka T, Koya T, Nakao M, Hagiwara H, Kamada R, Temma T, Tanaka S, Anzai T (2023) Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats. Front Cardiovasc Med 10:1005408. | ||
|info=https://pubmed.ncbi.nlm.nih.gov/36815024/ | |||
|authors=Koizumi Takuya, Watanabe Masaya, Yokota Takashi, Tsuda Masumi, Handa Haruka, Koya Jiro, Nishino Kotaro, Tatsuta Daishiro, Natsui Hiroyuki, Kadosaka Takahide, Koya Taro, Nakao Motoki, Hagiwara Hikaru, Kamada Rui, Temma Taro, Tanaka Shinya, Anzai Toshihisa | |||
|year=2023 | |||
|journal=Front Cardiovasc Med | |||
|abstract=Introduction: Recent studies have demonstrated that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM), in which oxidative stress due to increased reactive oxygen species (ROS) contributes to the pathogenesis of AF. We aimed to further investigate this, and examine whether the SGLT2-i empagliflozin suppresses mitochondrial-ROS generation and mitigates fibrosis. | |||
ย | |||
Methods: A high-fat diet and low-dose streptozotocin treatment were used to induce type-2 DM (T2DM) in Sprague-Dawley rats. The rats were randomly divided into three groups: control, DM, and DM treated with empagliflozin (30 mg/kg/day) for 8 weeks. The mitochondrial respiratory capacity and ROS generation in the atrial myocardium were measured using a high-resolution respirometer. Oxidative stress markers and protein expression related to mitochondrial biogenesis and dynamics as well as the mitochondrial morphology were examined in the atrial tissue. Additionally, mitochondrial function was examined in H9c2 cardiomyoblasts. Atrial tachyarrhythmia (ATA) inducibility, interatrial conduction time (IACT), and fibrosis were also measured. | |||
ย | |||
Results: Inducibility of ATA, fibrosis, and IACT were increased in rats with DM when compared to controls, all of which were restored by empagliflozin treatment. In addition, the rats with DM had increased mitochondrial-ROS with an impaired complex I-linked oxidative phosphorylation capacity. Importantly, empagliflozin seemed to ameliorate these impairments in mitochondrial function. Furthermore, empagliflozin reversed the decrease in phosphorylated AMPK expression and altered protein levels related to mitochondrial biogenesis and dynamics, and increased mitochondrial content. Empagliflozin also improved mitochondrial function in H9c2 cells cultured with high glucose medium. | |||
ย | |||
Discussion: These data suggest that empagliflozin has a cardioprotective effect, at least in part, by reducing mitochondrial ROS generation through AMPK signaling pathways in the atrium of diabetic rats. This suggests that empagliflozin might suppress the development of AF in T2DM. | |||
|keywords=SGLT2 inhibitor; diabetes; empagliflozin; mitochondria; reactive oxygen species | |||
|mipnetlab=JP Sapporo Yokota T | |||
}} | |||
{{Labeling | |||
|area=Respiration | |||
|diseases=Cardiovascular, Diabetes | |||
|organism=Rat | |||
|tissues=Heart | |||
|preparations=Permeabilized tissue | |||
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase | |||
|topics=ADP, Inhibitor, Redox state, Substrate | |||
|couplingstates=LEAK, OXPHOS | |||
|instruments=Oxygraph-2k, O2k-Fluorometer | |||
|additional=JP, 2023-02 | |||
}} | |||
{{OROBOROS_header_page_name}} | {{OROBOROS_header_page_name}} | ||
{{Template:OROBOROS Slogan}} | {{Template:OROBOROS Slogan}} |
Revision as of 08:47, 27 February 2023
Koizumi T, Watanabe M, Yokota T, Tsuda M, Handa H, Koya J, Nishino K, Tatsuta D, Natsui H, Kadosaka T, Koya T, Nakao M, Hagiwara H, Kamada R, Temma T, Tanaka S, Anzai T (2023) Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats. Front Cardiovasc Med 10:1005408. |
ยป https://pubmed.ncbi.nlm.nih.gov/36815024/
Koizumi Takuya, Watanabe Masaya, Yokota Takashi, Tsuda Masumi, Handa Haruka, Koya Jiro, Nishino Kotaro, Tatsuta Daishiro, Natsui Hiroyuki, Kadosaka Takahide, Koya Taro, Nakao Motoki, Hagiwara Hikaru, Kamada Rui, Temma Taro, Tanaka Shinya, Anzai Toshihisa (2023) Front Cardiovasc Med
Abstract: Introduction: Recent studies have demonstrated that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM), in which oxidative stress due to increased reactive oxygen species (ROS) contributes to the pathogenesis of AF. We aimed to further investigate this, and examine whether the SGLT2-i empagliflozin suppresses mitochondrial-ROS generation and mitigates fibrosis.
Methods: A high-fat diet and low-dose streptozotocin treatment were used to induce type-2 DM (T2DM) in Sprague-Dawley rats. The rats were randomly divided into three groups: control, DM, and DM treated with empagliflozin (30 mg/kg/day) for 8 weeks. The mitochondrial respiratory capacity and ROS generation in the atrial myocardium were measured using a high-resolution respirometer. Oxidative stress markers and protein expression related to mitochondrial biogenesis and dynamics as well as the mitochondrial morphology were examined in the atrial tissue. Additionally, mitochondrial function was examined in H9c2 cardiomyoblasts. Atrial tachyarrhythmia (ATA) inducibility, interatrial conduction time (IACT), and fibrosis were also measured.
Results: Inducibility of ATA, fibrosis, and IACT were increased in rats with DM when compared to controls, all of which were restored by empagliflozin treatment. In addition, the rats with DM had increased mitochondrial-ROS with an impaired complex I-linked oxidative phosphorylation capacity. Importantly, empagliflozin seemed to ameliorate these impairments in mitochondrial function. Furthermore, empagliflozin reversed the decrease in phosphorylated AMPK expression and altered protein levels related to mitochondrial biogenesis and dynamics, and increased mitochondrial content. Empagliflozin also improved mitochondrial function in H9c2 cells cultured with high glucose medium.
Discussion: These data suggest that empagliflozin has a cardioprotective effect, at least in part, by reducing mitochondrial ROS generation through AMPK signaling pathways in the atrium of diabetic rats. This suggests that empagliflozin might suppress the development of AF in T2DM. โข Keywords: SGLT2 inhibitor; diabetes; empagliflozin; mitochondria; reactive oxygen species
โข O2k-Network Lab: JP Sapporo Yokota T
Labels: MiParea: Respiration
Pathology: Cardiovascular, Diabetes
Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase Regulation: ADP, Inhibitor, Redox state, Substrate Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k, O2k-Fluorometer
JP, 2023-02
O2k-Publications: Topics
- Mitochondria and Cell Research - the Oroboros Ecosystem
- ยป Please send us references on your Oroboros O2k applications for the list of O2k-Publications, which is updated by Bioblast editors and active wiki users. โ Contact: Mario Plangger
- ยป O2k-Publications alert - ยป Recent O2k-Publications
- ยป O2k-briefs
- ยป O2k-Publications - chronological: 4699
Mitochondrial physiology: MiP areas
# O2k-Publications MitoPedia: Comment O2k Total 1 mt-Medicine (363 entries) 363 516 2 Exercise physiology;nutrition;life style 755 1049 3 Comparative MiP;environmental MiP 324 476 4 Pharmacology;toxicology 843 1040 5 mt-Biogenesis;mt-density 248 331 6 Genetic knockout;overexpression 653 722 7 Instruments;methods 273 416
Pathological states
- Alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 Aging;senescence 275 417 2 Alzheimer's 71 94 3 Autism 7 11 4 Cancer 356 514 5 Cardiovascular 207 289 6 COPD 10 13 7 Diabetes 348 466 8 Inherited 64 99 9 Infectious 50 69 10 Myopathy 77 89 11 Neurodegenerative 169 235 12 Obesity 254 421 13 Parkinson's 67 104 14 Sepsis 74 85 15 Other 289 361
Stress conditions
- Alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 Cell death White, brown, beige fat tissue 93 156 2 Cryopreservation 41 67 3 Hypoxia 117 229 4 Ischemia-reperfusion 326 433 5 Oxidative stress;RONS 581 839 6 Permeability transition 71 96 7 Temperature: hypothermia; hyperthermia 91 112
Organisms
- Mammals
- Model organisms
# O2k-Publications MitoPedia: Comment O2k Total 1 Chicken (ยป Birds) 5 7 2 Zebrafish (ยป Fishes) 15 22 3 Drosophila (ยป Hexapods) 65 91 4 Caenorhabditis elegans (ยป Nematodes) 24 33 5 Artemia (ยป Crustaceans) 12 19 6 Saccharomyces cerevisiae (ยป Fungi) 61 88 7 Comparative MiP 324 476
- Non-mammals
# O2k-Publications MitoPedia: Comment O2k Total 1 Birds (ยป Chicken) 15 27 2 Reptiles turtles, lizards, snakes, crocodiles, alligators 13 18 3 Amphibians frogs, toads, salamanders 10 15 4 Fishes bony fishes, carilaginous fishes (sharks, rays, skates) and jawless fishes (hagfish, lampreys); ยป Zebrafish 116 153 5 Hexapods insects, springtails; ยป Drosophila 34 43 6 Crustaceans crabs, shrimp, barnacles, etc.; ยป Artemia 19 40 7 Annelids polychaetes, e.g. lugworm Arenicola marina, oligochaetes, leeches 3 20 8 Molluscs gastropods, cephalopods, bivalves 25 42 9 Nematodes ยป Caenorhabditis elegans 5 11 10 Other invertebrates urocordates (e.g. ascidians, sea squirts); cephalochordates (amphioxus, lancelets); echinoderms; chelicerates (e.g. spiders, scorpions, horseshoe crabs); myriapods (millipedes, centipedes); gastrotrichs; rotifers; ctenophores; nemerteans; tardigrades; platyhelminthes; cnidaria; porifera; ... 11 21 11 Fungi yeast, molds, mushrooms, etc.; ยป Saccharomyces cerevisiae 52 63 12 Plants 29 58 13 Protists amoebas, ciliates, trypanosomes, dinoflagellates, diatoms, green algae, etc. 42 59 14 Eubacteria true bacteria, cyanobacteria, spirochetes 25 51 15 Archaea archaebacteria 0 7
Tissues and cells
- Tissues - alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 Fat White, brown, beige fat tissue 187 262 2 Genital 92 123 3 Heart 723 935 4 Kidney 150 183 5 Liver 644 839 6 Lung;Gill 59 82 7 Nervous system 606 732 8 Skeletal muscle 1102 1366
- Cell types - alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 Blood cells 254 320 2 Endothelial;epithelial;mesothelial cell 259 294 3 Fibroblast 206 270 4 Islet cell;pancreas;thymus 54 66 5 Leukemia 22 25 6 Lymphocyte 58 76 7 Platelets 121 151 8 Stem cells 36 48
- Cell lines - alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 CHO 14 16 2 HEK 95 116 3 HeLa 38 55 4 Neuroblastoma 42 49 5 HUVEC 19 22 6 Macrophage-derived cell lines 26 37 7 Other cells and cell lines 292 338
Preparations
# O2k-Publications MitoPedia: Comment O2k Total 1 Living organism 53 248 2 Intact organ 23 38 3 Living cells 1162 1311 4 Permeabilized cells 714 752 5 Permeabilized tissue 1113 1207 6 Homogenate 375 419 7 Isolated mitochondria 1259 1566 8 SMP Submitochondrial particles 10 28 9 Chloroplasts 2 10 10 Enzyme 39 102 11 Oxidase and biochemical oxidation 39 49
Enzymes
- Alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 Adenine nucleotide translocase ANT 21 27 2 Complex I CI 460 606 3 Complex II;succinate dehydrogenase CII 410 637 4 Complex III CIII 300 362 5 Complex IV;cytochrome c oxidase CIV 405 496 6 Complex V;ATP synthase CV 219 266 7 mt-Inner membrane transporter 31 44 8 Marker enzyme 58 84 9 Supercomplex 48 77 10 TCA cycle and matrix dehydrogenases Tricarboxylic acid cycle 81 108 11 Uncoupling protein 60 66
Regulation
- Alphabetical order
# O2k-Publications MitoPedia: Comment O2k Total 1 ADP ADP kinetics 152 207 2 ATP production 78 123 3 Aerobic glycolysis 49 94 4 Amino acid 9 20 5 Calcium 106 179 6 Coupling efficiency;uncoupling 82 163 7 Cyt c Cytochrome c 42 56 8 Fatty acid FA substrate kinetics 127 159 9 Flux control 54 86 10 Inhibitor Inhibitor kinetics 131 169 11 Ion;substrate transport 64 115 12 mt-Membrane potential Mitochondrial membrane potential
- Bioblast links: Force and membrane potential - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
- Fundamental relationships
- ยป Force
- ยป Affinity
- ยป Flux
- ยป Advancement
- ยป Advancement per volume
- ยป Stoichiometric number
- Fundamental relationships
- mt-Membrane potential and protonmotive force
- ยป Uncoupler
- O2k-Potentiometry
- ยป O2k-Catalogue: O2k-TPP+ ISE-Module
- ยป O2k-Manual: MiPNet15.03 O2k-MultiSensor-ISE
- ยป TPP - O2k-Procedures: Tetraphenylphosphonium
- ยป Specifications: MiPNet15.08 TPP electrode
- ยป Poster
- ยป Unspecific binding of TPP+
- ยป TPP+ inhibitory effect
- O2k-Potentiometry
- O2k-Fluorometry
- ยป O2k-Catalogue: O2k-FluoRespirometer
- ยป O2k-Manual: MiPNet22.11 O2k-FluoRespirometer manual
- ยป Safranin - O2k-Procedures: MiPNet20.13 Safranin mt-membranepotential / Safranin
- ยป TMRM - O2k-Procedures: TMRM
- O2k-Fluorometry
- O2k-Publications
116 179 13 Oxygen kinetics 107 148 14 Q-junction effect 13 56 15 Redox state 58 98 16 Substrate Fuel substrate kinetics 181 236 17 Temperature Temperature dependence 73 100 18 Threshold;excess capacity 27 30 19 Uncoupler Uncoupler kinetics 55 70
Coupling-control
# O2k-Publications MitoPedia: Coupling-control states Comment O2k Total 1 P OXPHOS capacity Oxidative phosphorylation capacity, saturating [ADP] 2858 3087 2 R ROUTINE respiration Physiological state, living cells 892 979 3 E ET capacity Maximal noncoupled respiration 2061 2172 4 L LEAK respiration Resting state, non-phosphorylating respiration 2603 2762
Pathway control
# O2k-Publications MitoPedia: Electron-transfer-pathway states Comment O2k Total 1 F F-pathway control state Fatty acid oxidation, level 5 607 751 2 N N-pathway control state NADH-linked, level 4 2467 2615 3 S S-pathway control state Succinate-linked, level 3 1679 1787 4 Gp Gp-pathway control state Glycerophosphate-linked, level 3 156 182 5 DQ Duorquinol-linked, level 2 26 31 6 CIV Complex IV single step Ascorbate & TMPD, level 1 700 728 7 NS NS-pathway control state Convergent CI- and CII-linked electron flow to the Q-junction 1574 1631 8 Other 131 147 9 ROX Residual oxygen consumption includes non-mitochondrial respiration 1516 1568
MiPMap combinations - examples
- Examples for specific combinations
# O2k-Publications MitoPedia: Comment O2k Total 1 O2k-Publications: Human skeletal muscle 1102 1366 2 O2k-Publications: Human heart 723 935 3 O2k-Publications: Skeletal muscle - human vs mouse 39 48
- Browse data
O2k-Manuals and protocols and specific instrumental applications
# O2k-Publications MitoPedia: Comment O2k Total 1 Twin-Flow respirometry 0 21 2 Separate DatLab applications 29 35