Effect of testosterone on the regulation of p53 and p66Shc during oxidative stress damage in C2C12 cells

MILANESI, LORENA; PRONSATO, LUCÍA

STEROIDS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2016 vol. 106 p. 41 - 54

0039-128X

Accumulating evidence indicates that apoptosis is activated in the aged skeletal muscle, contributing tosarcopenia. We have previously demonstrated that testosterone protects against hydrogen peroxide(H2O2)-induced apoptosis in C2C12 muscle cells, at different levels: morphological, physiological, biochemicaland molecular. In the present study we observed that H2O2 induces the mitochondrial permeabilitytransition pore (mPTP) opening and exerts p53 activation in a time-dependent way, with amaximum response after 1?2 h of treatment. Testosterone treatment, prior to H2O2, reduces not onlyp53 phosphorylation but also p66Shc expression, activation and its mitochondrial localization, at thesame time that it prevents the mPTP opening. Furthermore, testosterone diminishes JNK and PKCbI phosphorylationinduced by H2O2 and probably contributing thus, to reduce the activation of p66Shc. Thus,the mPTP opening, p53, JNK and PKCbI activation, as well as p66Shc mRNA increase, induced by oxidativestress, were reduced by testosterone pretreatment. The data presented in this work show some of thecomponents upstream of the classical apoptotic pathway, that are activated during oxidative stressand that are points where testosterone exerts its protective action against apoptosis, exposing some ofthe puzzle pieces of the intricate network that aged skeletal muscle apoptosis represents.