?Testosterone inhibits the intrinsic apoptotic pathway induced by H2O2 in C2C12 skeletal muscle cells?.

PRONSATO, LUCÍA; BOLAND, RICARDO; MILANESI, LORENA

Puerto Madryn, Bs. As, Argentina.

Congreso; XLVI Reunión anual de la SAIB.; 2010

SAIB

TESTOSTERONE INHIBITS THE INTRINSIC APOPTOTIC PATHWAY INDUCED BY H2O2 IN C2C12 SKELETAL MUSCLE CELLS Pronsato L, Boland R, Milanesi L. Dpto. de Biología, Bioquímica y Farmacia, UNS. 8000 Bahía Blanca. lpronsato@criba.edu.ar Apoptosis, the process whereby cells die through an orchestrated self-destruction, occurs in response to environmental or developmental cues, cellular stresses and specific cell death signals. Mitochondria trigger the initial events of the intrinsic apoptotic pathway via release of proapoptotic proteins. In previous work we demonstrated that testosterone protected against H2O2-induced apoptosis in C2C12 cells. In this study, we identified molecular events that occur during the anti-apoptotic effects of testosterone. At short times of exposure to H2O2, cells exhibit ERK2, Akt and Bad phosphorylation and an increase of HSP70 levels. At longer treatment intervals with the apoptotic agent, dephosphorylation of the proteins mentioned before, cytochrome c release and PARP cleavage occurs. Treatment with testosterone prior to H2O2 induced Bad inactivation, translocation of HSP90 to mitochondria and a decrease in Bax levels, showing a protective role of the hormone and a putative modulation of the apoptotic intrinsic pathway. Moreover, we observed an extra nuclear localization of the androgen receptor (AR) in mitochondria and microsomes. The fact that simultaneous treatments with testosterone, H2O2 and the AR antagonist, flutamide, reduce the effects of the hormone on Bax and PARP proteins, points to a possible participation of a non-classical AR in the anti-apoptotic effect of testosterone.