Estradiol prevents release of cytochrome c from heart mitochondria after ischemia due to activation of estrogen receptors

Abstract

Estrogens are known to play a cardioprotective role in global myocardial ischemia–reperfusion. Our previous studies have shown that estradiol protects heart mitochondria from the loss of cytochrome c, increases mitochondrial functional activity and reduces apoptosis after 60 min of ischemia. In this study, we aimed to elucidate mechanism by which estrogens protect heart mitochondria during ischemia. The effect of estrogens on mitochondria might be related to binding of estrogen to the receptors alpha and beta or it might be direct. The experimental model of Langendorff-perfused rat heart, inhibitor of estrogens receptors (ER) alpha and beta (ICI 182780) and activator of ER beta DPN were used in order to determine the mechanism of cardioprotective action of estradiol on mitochondria after ischemia. We found that cytochrome c amount after 60 min of ischemia decreased by 25%, in ischemia-damaged mitochondria treated with 17β-estradiol (100 nM) the content of cytochrome c was not significantly different from control mitochondria; however, after pre-perfusion with ICI 182780 and estradiol, the amount of cytochrome c was decreased by 23%. Cytochrome c, released from mitochondria during ischemia, has accumulated in cytosol, this was also prevented by estradiol. However, pre-perfusion with ICI 182780 reversed the protective effect of estradiol. Also we have found that DPN similar to estradiol protected heart mitochondria from the loss of cytochrome c and increased respiration rate after 60 min ischemia. In conclusion, these results show that estradiol prevents release of cytochrome c from heart mitochondria to cytosol after ischemia due to activation of estrogen receptors.