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Difference between revisions of "Drahota 2014 Physiol Res"

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{{Publication
{{Publication
|title=Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M (2014) Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties. Physiol Res 63:1-11.
|title=Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M (2014) Biguanides inhibit Complex I, II and IV of rat liver mitochondria and modify their functional properties. Physiol Res 63:1-11.
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24182344 PMID: 24182344]
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24182344 PMID: 24182344]
|authors=Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M
|authors=Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M
|year=2014
|year=2014
|journal=Physiol Res
|journal=Physiol Res
|abstract=In this study, we focused on an analysis of biguanides effects on
|abstract=In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial Complex I but also Complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca<sup>2+</sup> ions. Our data might be in agreement with the hypothesis of SchΓ€fer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited Complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.
mitochondrial enzyme activities, mitochondrial membrane
potential and membrane permeability transition pore function.
We used phenformin, which is more efficient than metformin,
and evaluated its effect on rat liver mitochondria and isolated
hepatocytes. In contrast to previously published data, we found
that phenformin, after a 5 min pre-incubation, dose-dependently
inhibits not only mitochondrial complex I but also complex II and
IV activity in isolated mitochondria. The enzymes complexes
inhibition is paralleled by the decreased respiratory control index
and mitochondrial membrane potential. Direct measurements of
mitochondrial swelling revealed that phenformin increases the
resistance of the permeability transition pore to Ca<sup>2+</sup> ions. Our
data might be in agreement with the hypothesis of SchΓ€fer
(1976) that binding of biguanides to membrane phospholipids
alters membrane properties in a non-specific manner and,
subsequently, different enzyme activities are modified via lipid
phase. However, our measurements of anisotropy of fluorescence
of hydrophobic membrane probe diphenylhexatriene have not
shown a measurable effect of membrane fluidity with the 1 mM
concentration of phenformin that strongly inhibited complex I
activity. Our data therefore suggest that biguanides could be
considered as agents with high efficacy but low specifity.
|keywords=Metformin, Phenformin, Mitochondrial enzymes, Mitochondrial permeability transition pore, Membrane fluidity
|keywords=Metformin, Phenformin, Mitochondrial enzymes, Mitochondrial permeability transition pore, Membrane fluidity
|mipnetlab=CZ Hradec Kralove Cervinkova Z, CZ Prague Houstek J, CZ Prague Kalous M
|mipnetlab=CZ Hradec Kralove Cervinkova Z, CZ Prague Houstek J, CZ Prague Kalous M

Latest revision as of 12:24, 30 April 2021

Publications in the MiPMap
Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M (2014) Biguanides inhibit Complex I, II and IV of rat liver mitochondria and modify their functional properties. Physiol Res 63:1-11.

Β» PMID: 24182344

Drahota Z, Palenickova E, Endlicher R, Milerova M, Brejchova J, Vosahlikova M, Svoboda P, Kazdova L, Kalous M, Cervinkova Z, Cahova M (2014) Physiol Res

Abstract: In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial Complex I but also Complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca2+ ions. Our data might be in agreement with the hypothesis of SchΓ€fer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited Complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity. β€’ Keywords: Metformin, Phenformin, Mitochondrial enzymes, Mitochondrial permeability transition pore, Membrane fluidity

β€’ O2k-Network Lab: CZ Hradec Kralove Cervinkova Z, CZ Prague Houstek J, CZ Prague Kalous M


Labels: MiParea: Respiration, Pharmacology;toxicology 


Organism: Rat  Tissue;cell: Liver  Preparation: Homogenate, Isolated mitochondria 


Coupling state: OXPHOS  Pathway: N, S, CIV  HRR: Oxygraph-2k 

Metformin