Estradiol prevents release of cytochrome c from mitochondria and inhibits ischemia-induced apoptosis in perfused heart.
The study investigated whether estradiol can prevent release of cytochrome c from mitochondria and induction of apoptosis after 30 and 60 min stop-flow heart ischemia in Langendorff-perfused female rat hearts. Pre-perfusion of hearts with 100 nM 17beta-estradiol prevented the loss of cytochrome c from mitochondria, its accumulation in cytosol, and inhibition of respiration during ischemia. Estradiol strongly reduced activation of caspase-3-like activity and decreased DNA strand breaks in the nuclei of cardiomyocytes (measured by TUNEL staining). The results show that 17beta-estradiol prevents the ischemia-induced release of cytochrome c from mitochondria, subsequent inhibition of mitochondrial respiration, and inhibits caspase activation and apoptosis. Therefore, inhibition of the intrinsic, mitochondria-mediated apoptotic pathway may be one of the mechanisms by which estrogens protect the heart against ischemic damage.
Morkuniene
Ramune
R
Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania.
Arandarcikaite
Odeta
O
Borutaite
Vilmante
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism*; D053960:DNA Breaks; D053938:DNA Fragmentation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D004958:Estradiol; D045304:Cytochromes c