The role of mitogen-activated protein kinases in hydrogen peroxide-induced myogenic cell apoptosis

Abstract

Transplantation of autologous skeletal muscle-derived stem cells into injured heart may limit scar thinning and dilatation and improve myocardial function. Success of cellular cardiomyoplasty depends on the integration and survival of the engrafted cells in injured myocardial tissue. A great part of transplanted cells die in the first hours after transplantation as a consequence of activation and release of various bioactive substances such as reactive oxygen species (ROS) and cytokines in the damaged heart tissue. The purpose of this work was to elucidate the role of mitogen-activated kinases (MAPK) in ROS-induced myogenic cell apoptosis. Adult rabbit skeletal muscle stem cells were exposed to increasing concentrations of H2O2. We found that apoptotic concentrations of H2O2 transiently activated JNK and p38 MAP kinases, whereas the effect of adding H2O2 on ERK phosphorylation was negligible. Specific inhibition of ERK, JNK and p38 MAPK increased the apoptotic effect of 500–1000 μM H2O2. These results suggest the protective role of ERK, JNK and p38 MAP kinases in oxidative stress-induced myogenic cell apoptosis. Keywords: myogenic cells, MAP kinase, apoptosis