Estrogen Receptors, MAPKs and HSP27 Are Linked in the Antiapoptotic Effect of 17beta-estradiol in Skeletal Muscle Cells;¨.

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

Denver, colorado

Simposio; 31-The American Society for Bone and Mineral research.; 2009

The American Society for Bone and Mineral Research (ASBMR).

SU454 (PDF) We previously showed that 17b-estradiol (E2), at physiological concentrations, abrogates apoptosis in murine skeletal muscle C2C12 cells. It was demonstrated that the antiapoptotic action of the hormone is mediated by estrogen receptors (ERs), HSP27 and MAPKs. To further characterize the molecular mechanism activated by the steroid in muscle, in the present study we investigated relationships between ERs, MAPKs and HSP27. First, the protective action of E2 was evaluated in primary cultures of mouse skeletal muscle to validate the use of the C2C12 cell line. Comparable results were obtained. The role of ER in activation of ERKs and p38 MAPK by E2 was then studied in presence of ICI182780. By Western blot assays we found that ER participates in ERK2 but not in p38 MAPK phosphorylation. To confirm these results, similar experiments were carried out using C2C12 cells transfected with siRNAs against ER a and b. E2 activated ERK2 through ER a but neither isoform was involved in p38 MAPK phosphorylation. In addition, 17b-estradiol increased HSP27 expression. Evidence obtained showed that the protective role of the hormone requires the participation of HSP27 in C2C12 cells. Furthermore, immunocytochemical and co-immunoprecipitation assays demonstrated colocalization and interaction of HSP27 with ERs, indicating a role for HSP27 mediating the survival signaling of the steroid in muscle cells. These findings contribute to the knowledge of estrogen regulation of skeletal muscle metabolism.