Glucocorticoids decrease cytochrome c oxidase activity of isolated rat kidney mitochondria.
The importance of mitochondria is rising as a target in pathologic processes such as ischemia. We have investigated the effects of hydrocortisone, prednisolone, dexamethasone and triamcinolone on oxidative phosphorylation, Ca2+ fluxes, swelling and membrane potentials in isolated kidney mitochondria. The measurement of respiration state 3 showed a significant decrease in presence of glucocorticoids whereas the other respiration states were not modified. When mitochondria were uncoupled and either the complexes III and IV or the complex IV were stimulated, the O2 consumption was decreased by glucocorticoids. These results suggest the cytochrome c oxidase is a target of the glucocorticoid effect on the respiratory chain. Indeed, the other mitochondrial functions investigated were unchanged, ruling out a direct effect on Ca2+ fluxes or swelling. A regulation of cytochrome c oxidase activity by glucocorticoids will be of particular interest in pathology involving metabolic insult.
Simon
N
N
Départment de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France.
Jolliet
P
P
Morin
C
C
Zini
R
R
Urien
S
S
Tillement
J P
JP
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014221:Triamcinolone / Q000494:pharmacology
D005938:Glucocorticoids; D014221:Triamcinolone; D003907:Dexamethasone; D011239:Prednisolone; D003576:Electron Transport Complex IV; D002118:Calcium; D006854:Hydrocortisone