ROLE OF ERK1/2 AND p38 MAPKS IN THE ANTIAPOPTOTIC EFFECTS OF 17b-ESTRADIOL IN MUSCLE CELLS

RONDA ANA CAROLINA; VASCONSUELO ANDREA; BOLAND RICARDO

MAR DEL PLATA, BUENOS AIRES, ARGENTINA

Congreso; SAIB XLIII REUNIÓN ANUAL; 2007

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR

Estrogens exert antiapoptotic effects in various cell types, e.g. vascular endothelial, smooth muscle and breast cancer cells. It has been reported that ERK1/2 is involved in the antiapoptotic action of 17b-estradiol (E2). We have recently shown that E2 abrogates apoptosis in C2C12 murine skeletal muscle cells. Rapid stimulation of ERK1/2 and p38 MAPK was also observed in the same cell line. In the present work, we studied the function MAPKs in the protective effects of 17b-estradiol in C2C12 muscle cells. Immunocytochemical assays using the Mitotracker Red probe demonstrated that ERK1/2 activated by E2 localizes mainly in mitochondria. Incubation of the cells with 17b-estradiol (10-8 M) prior to treatment with H2O2 reversed the changes induced by this apoptotic agent on the phosphorylation of Akt and Bad, cytochrome c and Smac/Diablo release, caspase 3 and PARP cleavage, and morphological changes in the cells. Of relevance, the protective effect of E2 was abolished in presence of U0126 (ERK1/2 inhibitor) and SB203580 (p38 inhibitor), thereby involving ERK1/2 and p38 MAPKs as part of the mechanism that underlies the protective action of 17b-estradiol in muscle cells.