title: 17β-Estradiol Abrogates Apoptosis Inhibiting PKCδ, JNK, and p66Shc Activation in C2C12 Cells.
abstract: 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.
authors: INBIOSUR-CONICET, 8000, Bahía Blanca, Argentina.
authors: Anabela
authors: A
authors: La Colla
authors: INBIOSUR-CONICET, 8000, Bahía Blanca, Argentina.
authors: Ricardo
authors: R
authors: Boland
authors: INBIOSUR-CONICET, 8000, Bahía Blanca, Argentina.
authors: Andrea
authors: A
authors: Vasconsuelo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects; D032448:Myoblasts, Skeletal / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D011960:Receptors, Estrogen; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D004958:Estradiol; D006861:Hydrogen Peroxide; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases
keywords: 17β-ESTRADIOL; C2C12 MUSCLE CELLS; JNK; PKCδ; p66Shc