Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties

Title:

Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties

Creator:

Zdeněk Drahota, Paleníčková, Eliška, Endlicher, R., Marie Milerová, Brejchová, J., Vosahliková, M., Svoboda, P., Ludmila Kazdová, Martin Kalous, Cervinková, Z., and Monika Cahová

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:695e04d9-dc7f-4369-9d6a-27877a7cfaae
uuid:695e04d9-dc7f-4369-9d6a-27877a7cfaae

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, metformin, phenformin, mitochondrial enzymes, mitochondrial permeability transition pore, membrane fluidity, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print

Description:

In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeabili ty 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 prev iously published data, we found that phenformin, after a 5 min pr e-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 potent ial. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca 2+ ions. Our data might be in agreement with the hypothesis of Schäfer (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., Z. Drahota ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2014 Volume:63 | Number:1

Harvested from:

CDK

Metadata only:

false