17b-ESTRADIOL PREVENTS APOPTOSIS THROUGH ACTIVATION OF THE PI3K/Akt PATHWAY IN SKELETAL MUSCLE C2C12 CELLS

VASCONSUELO ANDREA A. AND BOLAND RICARDO L.

Rosario

Congreso; XXIV Reunion Cientifica Anual de la Asociacion Argentina de Osteologia y Metabolismo Mineral; 2006

In previous studies we demonstrated antiapoptotic effects of 17b-estradiol, at physiological concentrations, through non-classical estrogen receptors in apoptotic murine skeletal muscle C2C12 cells (myoblasts). Here we analyzed the participation of PI3K/Akt in the protective action of the hormone. Immunocytochemistry studies using confocal microscopy demonstrated activation of Akt by 17b-estradiol. Treatment with Ly294002 abolished the ability of the estrogen to activate Akt suggesting the participation of PI3K. In addition, Western blot assays using anti-PARP antibody showed an inhibitory effect of 17b-estradiol on the cleavage of PARP induced by H2O2 (1mM), which was abolished by Ly294002 (25 ìM) or Wortmanin (0.1 ìM). Moreover, Ly294002 (25 ìM) abrogates estrogen inhibition of cytochrome c release induced by H2O2. Thus, our studies indicate that the PI3K/Akt pathway is involved in the antiapoptotic effects of 17b-estradiol in C2C12 myoblastic cells. This mechanism may be involved in estrogen regulation of skeletal muscle growth, as apoptosis plays an important role controlling the number of myoblasts which undergo differentiation into mature myotubes.