No abstract

Abstract17b-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 H 2 O 2 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 H 2 O 2 , which preceded loss of mitochondrial membrane potential. In addition, it was observed that H 2 O 2 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. Key Words" 17b-estradiol " C2C12 skeletal myoblasts

17β-Estradiol (E ) protects several nonreproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E at physiological concentrations prevented apoptosis induced by H O in skeletal myoblasts, reverting PKCδ, JNK, and p66Shc activation and exerting a beneficial action over mitochondria. Since genomic actions underlying the regulation of nuclear gene transcription are a common property of this steroid, the present work characterizes the transcriptional activity modulated by E to exert its antiapoptotic effect. We report that E protects skeletal myoblasts against apoptosis induced by H O modulating p53 and FoxO transcription factors and then their target genes Bcl-2, Bim, Puma, PERP, and MDM2, without affecting Noxa gene. The results presented in this work support the notion that the transcription factors FoxO and p53 coordinate apoptosis in C2C12 cells, and deepens our knowledge about a putative molecular mechanism by which E exerts beneficial effects against oxidative stress in skeletal myoblasts. J. Cell. Biochem. 118: 104-115, 2017. © 2016 Wiley Periodicals, Inc.

17β-Estradiol (E2) protects several non-reproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E2 at physiological concentrations prevented apoptosis induced by H2O2 in skeletal myoblasts. As we have also demonstrated a clear beneficial action of this hormone on skeletal muscle mitochondria, the present work further characterizes the signaling mechanisms modulated by E2 that are involved in mitochondria protection, which ultimately result in antiapoptosis. Here, we report that E2 through estrogen receptors (ERs) inhibited the H2O2-induced PKCδ and JNK activation, which results in the inhibition of phosphorylation and translocation to mitochondria of the adaptor protein p66Shc. In conjunction, the inhibition by the hormone of this H2O2-triggered signaling pathway results in protection of mitochondrial potential membrane. Our results provide basis for a putative mechanism by which E2 exerts beneficial effects on mitochondria, against oxidative stress, in skeletal muscle cells.

No abstract