Dehydroepiandrosterone as an inducer of mitochondrial permeability transition.
This paper reports an investigation upon the effect of dehydroepiandrosterone (DHEA) on some mitochondrial membrane functions, such as electron transport, transmembrane electric gradient and calcium permeability. It was found that the hormone induced the efflux of accumulated matrix Ca(2+), inhibited Site I of the respiratory chain, as well as bringing about the collapse of the transmembrane potential, and mitochondrial swelling. Taking into account that cyclosporin A (CSA) inhibited Ca(2+) release and the collapse of the transmembrane potential, it is concluded that the hormone may induce the opening of a non-specific transmembrane pore. The mechanism of pore opening is ascribed to peroxidation of the membrane lipid bilayer. It should be mentioned that estrone, even at the concentration of 200 microM, failed to reproduce the behavior of dehydroepiandrosterone on mitochondrial functions.
Correa
Francisco
F
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Tlalpan, Mexico, D.F. 014080, Mexico.
García
Noemí
N
García
Gerardo
G
Chávez
Edmundo
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D016572:Cyclosporine / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007672:Kidney Cortex / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D019802:Succinic Acid / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D012710:Serum Albumin, Bovine; D004970:Estrone; D003687:Dehydroepiandrosterone; D016572:Cyclosporine; D019802:Succinic Acid; D002118:Calcium