17B-ESTRADIOL INHIBITS APOPTOSIS THROUGH ACTIVATION OF MAPKS AND ESTROGEN RECEPTOR IN MUSCLE CELLS

RONDA ANA; VASCONSUELO ANDREA; BOLAND RICARDO

VILLA CARLOS PAZ, CORDOBA, ARGENTINA

Congreso; SAIB XLIV REUNION ANUAL; 2008

Reunión Anual de la Sociedad Argentina en Investigación Bioquímica y Biología Molecular (SAIB)

17beta-estradiol (E2) can sustain survival or induce apoptosis depending on the biological context of cells. We showed that E2 abrogates apoptosis in C2C12 cells involving estrogen receptors ERalpha and EReta at least by two different ways. One of them involves PI3K/Akt/BAD activation, which depends on both ERs. The other relates to a protective effect on mitochondria and involves mainly ERbeta. ERK1/2 and p38 MAPK were implicated in both mechanisms. In view of this evidence, we studied the role of ERs in the activation of MAPKs by E2. First, we evaluated by Western blot assays the activation of ERK1/2 and p38 MAPK by E2 in presence of the antagonist ICI182780. We found that ER participates in ERK1/2 but not in p38 MAPK phosphorylation. The same experiments performed with C2C12 cells transfected with siRNAs against the ER alpha and beta isoforms showed that E2 activates ERK1/2 through ERalpha. In addition, studies with E2-BSA indicated that E2-induced phosphorylation of MAPKs is not related to the participation of receptors localized in the plasma membrane. To validate the use of the C2C12 cell line, we evaluated the function of MAPKs in the antiapoptotic action of E2 in primary cultures of mouse skeletal muscle cells. Comparable results were obtained. Altogether, these findings raise the possibility that abnormal regulation of apoptosis may play a role in estrogen-dependent sarcopenia.