PROTECTIVE EFFECT OF 17beta-ESTRADIOL AND TESTOSTERONE AGAINST APOPTOSIS INVOLVING FOXOs AND P53-RELATED GENES IN SKELETAL MUSCLE CELLS

LA COLLA A,; MILANESI L,; PRONSATO L,; VASCONSUELO A,; LINCOR D,

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Científica de Investigación Clínica; 2016

SAIC

In aged skeletal muscle, a prominent apoptosis associated to a deficit of sex hormones is observed, contributing to the loss of muscle mass and strength, pathology known as sarcopenia. Previously we have demonstrated the protective effect, at morphological, physiological, biochemical and molecular level, of both 17β-estradiol (E2) and Testosterone (T) against H2O2-induced apoptosis in C2C12 skeletal muscle cell line. It has been established that the exposure of these cells to H2O2 represents a comparable phenotype to aged skeletal muscle, constituting a useful tool for the study of sarcopenia. Since genomic actions underlying the regulation of nuclear gene transcription are a classical mechanism of action of these hormones, we studied the transcriptional activity modulated by E2 and T in order to understand the molecular mechanisms involved in the antiapoptotic action of these steroids. We reported that the hormones protect skeletal myoblasts against apoptosis induced by H2O2 by modulating p53 and FoxO transcription factors and then, their target genes Bcl-2, Bim, Puma, PERP and MDM2, without affecting Noxa gene. Furthermore, ERK and JNK kinases have been demonstrated to be linked to FoxOs phosphorylation and thus its subcellular distribution and activation. The results presented in this work support the notion that E2 and T modulate the oxidative stress-induced apoptosis in skeletal muscle involving the transcription factors FoxO and p53. Altogether , these data expose some of the puzzle pieces of the intricate network that hormonal regulation of skeletal muscle apoptosis represents.