Direct antioxidant and protective effect of estradiol on isolated mitochondria.
Estrogens have antioxidant properties which are due to their ability to bind to estrogen receptors and to up-regulate the expression of antioxidant enzymes via intracellular signalling pathways. Mitochondria are key organelles in the development of age-associated cellular damage. Recently, estrogen receptors were identified in mitochondria. The aim of this paper was to test whether estradiol directly affects mitochondria by preventing oxidative stress and protecting frail mitochondria. Incubation with estradiol at normal intracellular concentrations prevents the formation of reactive oxygen species by mitochondria in a saturable manner. Moreover, estradiol protects mitochondrial integrity as indicated by an increase in mitochondrial membrane potential. It also prevents the apoptogenic leakage of cytochrome c from mitochondria and as a result the mitochondrial content of this cytochrome c is maintained high. Thus, estradiol prevents the onset of the mitochondrial pathway of apoptosis by a direct effect on the organelle. Genistein, a phytoestrogen present at high concentration in soy, mimics the protective effect of estradiol by both decreasing the rate of formation of reactive oxygen species and preventing the release of cytochrome c from mitochondria.
Borrás
Consuelo
C
Department of Physiology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibáñez 17, 46010 Valencia, Spain.
Gambini
Juan
J
López-Grueso
Raúl
R
Pallardó
Federico V
FV
Viña
Jose
J
D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D004958:Estradiol; D045304:Cytochromes c