α-Syntrophin is involved in the survival signaling pathway in myoblasts under menadione-induced oxidative stress

Dystrophin-deficient muscle is known to be more vulnerable to oxidative stress, but not much is known about the signaling pathway(s) responsible for this phenomenon. alpha-Syntrophin, a component of the dystrophin-glycoprotein complex, can function as a scaffold protein because of its multiple protein interaction domains. In this study, we investigated the role of alpha-syntrophin in C2 myoblasts under menadione-induced oxidative stress. We found that the protein level of alpha-syntrophin was elevated when cells were exposed to menadione. To investigate the function of alpha-syntrophin during oxidative stress, we established alpha-syntrophin-overexpressing and knockdown cell lines. The alpha-syntrophin-overexpressing cells were resistant to the menadione-induced oxidative stress. In addition, survival signalings such as protein kinase B (Akt) phosphorylation and the Bcl-2/BAX ratio were increased in these cells. On the other hand, apoptotic signals such as cleavage of caspase-3 and poly ADP ribose polymerase (PARP) were increased in the alpha-syntrophin knockdown cells. Furthermore, Ca2+ influx, which is known to increase when cells are exposed to oxidative stress, decreased in the alpha-syntrophin-overexpressing cells, but increased in the knockdown cells. These results suggest that alpha-syntrophin plays a pivotal role in the survival pathway triggered by menadione-induced oxidative stress in cultured myoblasts. (C) 2016 Elsevier Inc. All rights reserved.