title: Estradiol exerts antiapoptotic effects in skeletal myoblasts via mitochondrial PTP and MnSOD.
abstract: 17β-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.
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahía Blanca, Argentina.
authors.forename: Anabela
authors.initials: A
authors.lastname: La Colla
authors.forename: Andrea
authors.initials: A
authors.lastname: Vasconsuelo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Boland
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D004958:Estradiol; D013482:Superoxide Dismutase