Mitochondria play an important role in 17beta-estradiol attenuation of H(2)O(2)-induced rat endothelial cell apoptosis.
Studies have shown salutary effects of 17beta-estradiol following trauma-hemorrhage on different cell types. 17beta-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17beta-estradiol will maintain mitochondrial function and will have protective effects against H(2)O(2)-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H(2)O(2), a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17beta-estradiol. Flow cytometry analysis revealed H(2)O(2)-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17beta-estradiol resulted in an approximately 40% reduction in apoptosis. This protective effect of 17beta-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17beta-estradiol-mediated attenuation of H(2)O(2)-induced mitochondrial condensation. Western blot analysis demonstrated that H(2)O(2)-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17beta-estradiol. These findings suggest that 17beta-estradiol attenuated H(2)O(2)-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria.
Lu
Ailing
A
Center for Surgical Research, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Frink
Michael
M
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Hubbard
William J
WJ
Rue
Loring W
LW
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020011:Protective Agents; D004958:Estradiol; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; D020169:Caspases