Anti-apoptotic effects of 17beta-estradiol through estrogen receptors in skeletal muscle cells.?

VASCONSUELO, ANDREA; MILANESI, LORENA; BOLAND, RICARDO

Mar del Plata, Bs. As., Argentina

Congreso; XLIII Reunion anual de la SAIB.; 2007

In this study we report that 17â-estradiol (E2), through estrogen receptors with non-nuclear localization, e.g. mitochondria, endoplasmic reticulum and Golgi, can regulate apoptosis in mouse skeletal muscle C2C12 cells. E2, at physiological concentrations, abrogates DNA damage, PARP cleavage and cytochrome c release induced by H2O2 or etoposide. This protective action of the steroid involves fast activation of the PI3K/Akt/Bad pathway. Blocking experiments with specific antibodies and siRNAs against the estrogen receptor á (ER á) and â (ER â) isoforms, revealed that ER â mediates the mitochondrial protection by the hormone to a greater extent than ERá. On the other hand, both ER isoforms mediate to the same extent PI3K/Akt activation, suggesting different degree of participation of each isoform depending on the step of the apoptotic/survival pathway evaluated. Furthermore, it was shown that the protective role of the hormone also involves heat shock protein 27 (HSP27). E2 at longer exposure times increased the expression of HSP27. Immunocytochemistry and co-immunoprecipitation assays demonstrated co-localization and interaction of HSP27 with ERs in mitochondria. Altogether, these results suggest that the antiapoptotic signal triggered by 17â-estradiol in muscle cells is mediated by ER â and á and involves rapid activation of PI3K/Akt and the participation of HSP27.