Effects of tamoxifen on the electron transport chain of isolated rat liver mitochondria.
Tamoxifen (and 4-hydroxytamoxifen), a nonsteroidal triphenylethylene antiestrogenic drug widely used in the treatment of breast cancer, interacts strongly with the respiratory chain of isolated rat liver mitochondria. The drug acts as both an uncoupling agent and a powerful inhibitor of electron transport. Tamoxifen brings about a collapse of the membrane potential. Enzymatic assays and spectroscopic studies indicate that tamoxifen inhibits electron transfer in the respiratory chain at the levels of complex III (ubiquinol-cytochrome-c reductase) and, to a lesser extent, of complex IV (cytochrome-c oxidase). The activities can be restored by the addition of diphosphatidylglycerol, a phospholipid implicated in the functioning of the respiratory chain complexes.
Tuquet
C
C
Université Pierre et Marie Curie, Laboratoire de Biologie Cellulaire Végétale, Paris, France.
Dupont
J
J
Mesneau
A
A
Roussaux
J
J
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*
D013629:Tamoxifen; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV