Effects of testosterone on apoptosis in C2C12 murine skeletal muscle cells

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

Bahia Blanca

Jornada; II Jornada anual de Intercambio de becarios y tesistas en el CONICET Bahía Blanca "Salud y Alimentación"; 2014

In aged skeletal muscle, a prominent apoptosis associated to a deficit of sex hormones is observed, contributing to the pathogenesis of sarcopenia. We have demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12, murine skeletal muscle cell line, involving the androgen receptor (AR) with classical (nuclear) and non-classical (mitochondria and microsomes) localization. The aim of our research is to deepen the understanding of the antiapoptotic actions of the hormone in muscle. We observed that at short times of exposure to H2O2, C2C12 exhibit a defense response showing ERK, Akt and Bad phosphorylation, remaining in these state until 2 hours. Simultaneously, and during the 4 hours of H2O2 treatment, phosphorylation of proapoptotic protein JNK (1, 2 and 3) is observed. Using Real Time PCR, an increase in mRNA levels of apoptotic proteins were detected while antiapoptotic proteins undergo fluctuating changes during H2O2 exposure. Testosterone treatment prior to H2O2 maintains Akt phosphorylated throughout the time and reduces JNK phosphorylation and expression of apoptotic proteins. Moreover, the hormone reduces the activation of the proapoptotic protein p66Sshc and blocks its mitochondrial localization, induced by H2O2. The data obtained provide insights into the molecular basis of sex hormone-dependent sarcopenia.