AR, ER, MNSOD and COXIV in 17beta-estradiol and testosterone antiapoptotic effects in C2C12 cells.

PRONSATO, LUCÍA; LA COLLA, ANABELA; RONDA, ANA C; MILANESI, LORENA; VASCONSUELO, ANDREA; BOLAND, RICARDO

Mendoza

Congreso; Reunión anual de la SAIB.; 2012

SAIB

17b-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. Here we demonstrate that E2 up-regulates the expression and activity of manganese superoxide dismutase (MnSOD) while increases the activity of cytochrome c oxidase IV (COXIV) without changes in its expression. Pharmacological and immunological assays indicate that the estrogen receptor (ER) mediates these events. In addition, the expression of MnSOD and the activity of COXIV decrease when cells are treated with H2O2, effects that are reversed with E2 pretreatment. Experiments with the antagonist flutamide involve 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 an AR translocation from membrane to inner cellular compartments. Our studies deepen the knowledge of the molecular basis of myopathies associated with deregulation of apoptosis by hormonal deficit states.