title: Peroxynitrite induces degradation of myosin heavy chain via p38 MAPK and muscle-specific E3 ubiquitin ligases in C2 skeletal myotubes.
abstract: Oxidative stress and inflammation play an important role in the catabolism of skeletal muscles. Recently, cigarette smoke (CS) was shown to stimulate muscle catabolism by activation of p38 MAPK and up-regulation of the muscle-specific E3 ubiquitin ligases (E3s) atrogin-1 and MuRF1 which are over-expressed during muscle atrophy. Peroxynitrite (ONOO-), an oxidative ingredient of CS, also produced during oxidative stress and inflammation, was previously shown to induce ubiquitination and degradation of muscle proteins. To investigate the involvement of p38 MAPK and the muscle-specific E3s in ONOO--induced muscle catabolism, C2 myotubes, differentiated from a myoblast cell line, were exposed to ONOO- (25 μM) in a time-dependent manner. Following exposure, degradation of myosin heavy chain (MyHC) and actin, activation of p38 MAPK, and levels of atrogin-1 and MuRF1 were studied by Western blotting. Peak phosphorylation of p38 MAPK was observed at 1 h of ONOO- exposure. ONOO- caused a significant increase in the levels of atrogin-1 and MuRF1. In accordance, a significant decrease in MyHC levels was observed in a time-dependent manner. These findings support previous studies in which the catabolic effects of ONOO- were shown. In addition, ONOO- was demonstrated to induce degradation of muscle proteins by activation of p38 MAPK and up-regulation of the muscle-specific E3s atrogin-1 and MuRF1.
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Efron St., 9649, Bat Galim, Haifa, 31096, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Rom
authors.forename: S
authors.initials: S
authors.lastname: Kaisari
authors.forename: A Z
authors.initials: AZ
authors.lastname: Reznick
authors.forename: D
authors.initials: D
authors.lastname: Aizenbud
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009124:Muscle Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010766:Phosphorylation; D059748:Proteolysis; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C519276:myosin heavy chain-1, mouse; D030421:Peroxynitrous Acid; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D048051:p38 Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains