title: Cigarette smoke and muscle catabolism in C2 myotubes.
abstract: Previous studies have revealed evidence of muscular damage and up-regulation of genes associated with impaired muscle maintenance in smokers. Cigarette smoking has also been associated with sarcopenia, the age-related loss of muscle mass and strength. In order to investigate the cellular mechanisms by which cigarette smoke (CS) promotes muscle catabolism, C2 myotubes from an in vitro skeletal muscle cell line, were exposed to different levels of whole vapor phase CS using a controlled CS exposure apparatus. Exposure of C2 myotubes to CS caused a reduction in diameter of myotubes and a time- and dose-dependent degradation of myosin heavy chain. Also, CS exposure resulted in increased intracellular oxidative stress and p38 MAPK phosphorylation, which led to up-regulation of the muscle specific E3 ubiquitin ligases: MAFbx/atrogin-1 and MuRF1. Pretreatment with the antioxidant N-acetylcysteine and inhibition of p38 MAPK by SB203580 prevented CS induced catabolism. In conclusion, our results demonstrate that exposure of skeletal myotubes to CS leads to increased oxidative stress and activation of the p38 MAPK pathway resulting in muscle cell atrophy and breakdown of muscle protein mediated by muscle specific E3 ubiquitin ligases. Our findings provide a possible molecular mechanism for the catabolic effects of CS in skeletal muscle.
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport, Technion - Israel Institute of Technology, Bat Galim, Haifa, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Rom
authors.forename: Sharon
authors.initials: S
authors.lastname: Kaisari
authors.forename: Dror
authors.initials: D
authors.lastname: Aizenbud
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Reznick
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; D009124:Muscle Proteins; D011725:Pyridines; D014028:Tobacco Smoke Pollution; D000070584:Tripartite Motif Proteins; 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; C093642:SB 203580; D000111:Acetylcysteine