?17b-estradiol abrogates apoptosis in skeletal muscle cells through extra nuclear estrogen receptors.?

VASCONSUELO, ANDREA; MILANESI, LORENA; RUSSO DE BOLAND, ANA; BOLAND, RICARDO

Honolulu, Hawai

Congreso; 29th Annual Meeting of the American Society for Bone and Mineral Research; 2007

American Society for Bone and Mineral Research

T196 (PDF) Although there is evidence showing that estrogens regulate apoptosis in various cellular systems, the underlying molecular mechanism is not well understood. The present study demonstrates that 17b-estradiol, at physiological concentrations, abrogates apoptosis in mouse skeletal muscle C2C12 cells through estrogen receptors (ERs) with non-classical localization. Specific antibodies against ER a or b and silencing of ERs with ER a and b short interference RNAs (siRNAs) inhibited this protective action, which involved PI3K/Akt activation and BAD phosphorylation. Apoptosis inhibition by 17b-estradiol was stronger when ER b was blocked, suggesting that the b isoform mediates to a greater extent than the a isoform the antiapoptotic effects of the steroid hormone. Expression and subcellular distribution of ER a and b in extra nuclear compartments (mitochondria, endoplasmic reticulum and Golgi) of C2C12 cells were confirmed by competitive binding assays, conventional and confocal fluorescence microscopy, silencing of ERs with siRNAs and RT-PCR using specific primers. These results indicate that 17b-estradiol exerts antiapoptotic effects in skeletal muscle cells mediated by estrogen receptors with extra nuclear localization. <!--[if !supportEmptyParas]--> <!--[endif]-->