Anti-apoptotic effects of 17beta-estradiol in skeletal muscle cells mediated by the b isoform of estrogen receptor?.

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

Buenos Aires, Argentina

Congreso; XXII Reuni¨®n Anual de la AAOMM; 2007

Asociaci¨®n Argentina de Osteolog¨ªa y Metabolismo Mineral

Anti-apoptotic effects of 17¦Â-estradiol in skeletal muscle cells mediated by the B isoform of estrogen receptor Vasconsuelo AA, Milanesi LM, Ronda AC, Russo de Boland AJ, Boland RL. Dpto de Biolog¨ªa, Bioqu¨ªmica y Farmacia, Universidad Nacional del Sur, 8000 Bahia Blanca, Argentina Here we report that 17¦Â-estradiol, through estrogen receptors with non-nuclear localization, e.g. mitochondria, endoplasmic reticulum and Golgi, can regulate apoptosis in mouse skeletal muscle C2C12 cells. 17¦Â-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. Within the same short time interval, the hormone increases phosphorylation of ERK 1/2 and p38 MAPK and induces translocation of ERK 1/2 into mitochondria. Evidence was obtained suggesting that the ERK 1/2 and PI3K/Akt/Bad pathways play a role in the antiapoptotic effects of 17¦Â-estradiol at the mitochondria level. Blocking experiments with specific antibodies and siRNAs against the estrogen receptor ¦Á (ER¦Á) and ¦Â (ER¦Â) isoforms, revealed that ER¦Â mediates to a greater extent than ER¦Á the antiapoptotic effects of 17¦Â-estradiol. Also, it was shown that the protective role of the hormone requires the participation of heat shock protein 27 (HSP27). 17¦Â-Estradiol rapidly induced phosphorylation of HSP27 and at longer exposure times increased its expression. Immunocytochemistry and co-immunoprecipitation assays demonstrated colocalization and interaction of phosphorylated and nonphosphorylated forms of the chaperone with ER¦Â in mitochondria. Altogether, these results suggest that the antiapoptotic signal triggered by 17¦Â-estradiol is mediated by ER¦Â and requires rapid activation of Akt and ERK 1/2 and ABSTRACTS / Bone 41 (2007) S1¨CS13 S3 the participation of HSP27. The data provide basis for the sarcopenia associated to estrogen deficit states.