ANTI-APOPTOTIC EFFECTS OF 17β-ESTRADIOL THROUGH ESTROGEN RECEPTORS IN SKELETAL MUSCLE CELLs

VASCONSUELO A.; MILANESI L,; BOLAND R

Mar Del Plata

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

In this study we report that 17β-estradiol, through estrogen receptors with non-nuclear localization, e.g. mitochondria, endoplasmic reticulum and Golgi, can regulate apoptosis in mouse skeletal muscle C2C12 cells. 17β-estradiol, 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 α (ER α) and β (ER β) isoforms, revealed that ER β mediates the mitochondrial protection by the hormone to a greater extent than ERα. On the other hand, both ER isoforms mediate 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). 17β-estradiol at longer exposure times increased its expression. 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 17β-estradiol in muscle cells is mediated by ER β and α and involves rapid activation of PI3K/Akt and the participation of HSP27.