PROTECTIVE ROLE OF 17beta-ESTRADIOL IN APOPTOSIS OF SKELETAL MUSCLE

ANDREA VASCONSUELO; ANA CAROLINA RONDA; LA COLLA, ANABELA; RICARDO BOLAND

Congreso; AAOMM, XXVIII Reunión Anual. Asociación Argentina de Osteología y Metabolismo Mineral; 2011

We previously described a non classical localization for both estrogen receptors (ERs) in the C2C12 cell line and in mouse skeletal muscle tissue. ERbeta was exclusively detected in mitochondria and ERalpha in the perinuclear and mitochondrial compartments. Since mitochondria are key organelles in apoptosis, this subcellular location of ERs could be associated with the regulation of apoptosis of muscle cells by 17beta-estradiol (E2). Thus, we demonstrated that E2, at physiological concentrations, abrogates H2O2 induced-apoptosis through both ERalpha and ERbeta. Moreover, the mechanism activated by E2 in this protective action involved PI3K/Akt/Bad and MAPKs pathways and HSP27. We found that the steroid abrogates DNA damage, PARP and caspase-3 cleavage, cytochrome c and Smac/DIABLO release from mitochondria, induced by H2O2. Now, we perform flow cytometry studies with the cationic dye JC-1, showing that H2O2 induces a decrease in mitochondrial membrane potential, which is prevented by E2. In view that the loss of mitochondrial membrane potential could be due to the continuous mitochondrial permeability transition pore (MPTP) activation, we evaluated its functionality with calcein-AM by microscopy. We evidenced loss of green mitochondrial calcein fluorescence in cells treated with H2O2. However, this loss of fluorescence was prevented when the cells were preincubated with E2 and then treated with H2O2. Our studies have shown an important role of E2 in the regulation of apoptosis in muscle cells with a clear action at mitochondrial level. These findings could be important to overcome myopathies due to dysregulated apoptosis by disorders in estrogen metabolism.