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

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

JOURNAL OF BONE AND MINERAL RESEARCH

AMER SOC BONE & MINERAL RES

Año: 2007 p. 278 - 278

0884-0431

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.