title: α-Syntrophin is involved in the survival signaling pathway in myoblasts under menadione-induced oxidative stress.
abstract: 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. α-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 α-syntrophin in C2 myoblasts under menadione-induced oxidative stress. We found that the protein level of α-syntrophin was elevated when cells were exposed to menadione. To investigate the function of α-syntrophin during oxidative stress, we established α-syntrophin-overexpressing and knockdown cell lines. The α-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 α-syntrophin knockdown cells. Furthermore, Ca(2+)influx, which is known to increase when cells are exposed to oxidative stress, decreased in the α-syntrophin-overexpressing cells, but increased in the knockdown cells. These results suggest that α-syntrophin plays a pivotal role in the survival pathway triggered by menadione-induced oxidative stress in cultured myoblasts.
authors.affiliation: Department of Biological Science, College of Natural Sciences, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Biological Science, College of Natural Sciences, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Natural Sciences, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Biological Science, College of Natural Sciences, Ajou University, Suwon 443-749, Republic of Korea. Electronic address: hsunkim@ajou.ac.kr.
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D042541:Intracellular Space / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D055550:Protein Stability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D024483:Vitamin K 3 / Q000633:toxicity*
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C091825:syntrophin alpha1; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D002118:Calcium
keywords: Apoptosis; Calcium imaging; Menadione; Myoblast; Oxidative stress; α-Syntrophin