Estradiol exerts antiapoptotic effects in skeletal myoblasts via mitochondrial PTP and MnSOD

17 beta-Estradiol (E-2) protects several non-reproductive tissues from apoptosis, including skeletal muscle. We have shown that E-2 at physiological concentrations prevented apoptosis induced by H2O2 in C2C12 skeletal myoblasts. As we also demonstrated the presence of estrogen receptors in mitochondria, the present work was focused on the effects of E-2 on this organelle. Specifically, we evaluated the actions of E-2 on the mitochondrial permeability transition pore (MPTP) by the calcein-acetoxymethylester/cobalt method using fluorescence microscopy and flow cytometry. Pretreatment with E-2 prevented MPTP opening induced by H2O2, which preceded loss of mitochondrial membrane potential. In addition, it was observed that H2O2 induced translocation of Bax to mitochondria; however, in the presence of the steroid this effect was abrogated suggesting that members of the Bcl-2 family may be regulated by E-2 to exert an antiapoptotic effect. Moreover, E-2 increased mitochondrial manganese superoxide dismutase protein expression and activity, as part of a mechanism activated by E-2 that improved mitochondrial performance. Our results suggest a role of E-2 in the regulation of apoptosis with a clear action at the mitochondrial level in C2C12 skeletal myoblast cells.