INVOLVEMENT OF AR, ER, PKCgama, JNK AND MnSOD IN 17b-ESTRADIOL AND TESTOSTERONE ANTIAPOPTOTIC EFFECTS IN C2C12 SKELETAL MUSCLE CELLS

PRONSATO, LUCIA; LA COLLA, ANABELA; MILANESI, LORENA; BOLAND, RICARDO; VASCONSUELO, ANDREA

BsAs

Congreso; Reunion anual de la AAOMM; 2013

AAOMM

1B-Estradiol (E2) and Testosterone (T) exert actions in most tissues, including skeletal muscle. In aging, this tissue can present pathologies as sarcopenia which is associated to low hormone levels that cause a deregulation of apoptosis. We previously showed that E2 and T inhibit H2O2 - induced apoptosis in C2C12 cells. The aim of our research is to deepen the understanding of the molecular mechanisms involved in the antiapoptotic action of both hormones. Here we demonstrate that E2 up-regulates the expression and activity of manganese superoxide dismutase (MnSOD). Pharmacological and immunological assays indicate that the estrogen receptor (ER) mediates these events. In addition, the expression of MnSOD decreases when cells are treated with H2O2, effects that are reversed with E2 pretreatment. Moreover, we showed that the apoptotic action of hydrogen peroxide requires PKC and JNK activation which is abolished when the cells were pretreated with E2. Experiments with the antagonist flutamide involved the androgen receptor (AR) in the antiapoptotic action of T. Biochemical and immunological data support mitochondrial and microsomal localization of the AR in the C2C12 cells. Sucrose gradient fractionation demonstrates its presence in rafts and caveolae. Besides, the AR interacts with caveolin-1, association that is lost after T treatment, suggesting AR translocation from the membrane to inner cellular compartments. Our studies contribute to elucidate the mechanism by which these hormones regulate signaling cascades, throwing light on the molecular basis of myopathies associated with deregulation of apoptosis by sex hormone deficiency states.