title: The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes.
abstract: The toxic aldehydes acetaldehyde and acrolein were previously suggested to damage skeletal muscle. Several conditions in which exposure to acetaldehyde and acrolein is increased were associated with muscle wasting and dysfunction. These include alcoholic myopathy, renal failure, oxidative stress, and inflammation. A main exogenous source of both acetaldehyde and acrolein is cigarette smoking, which was previously associated with increased muscle catabolism. Recently, we have shown that exposure of skeletal myotubes to cigarette smoke stimulated muscle catabolism via increased oxidative stress, activation of p38 MAPK, and upregulation of muscle-specific E3 ubiquitin ligases. In this study, we aimed to investigate the effects of acetaldehyde and acrolein on catabolism of skeletal muscle. Skeletal myotubes differentiated from the C2 myoblast cell line were exposed to acetaldehyde or acrolein and their effects on signaling pathways related to muscle catabolism were studied. Exposure of myotubes to acetaldehyde did not promote muscle catabolism. However, exposure to acrolein caused increased generation of free radicals, activation of p38 MAPK, upregulation of the muscle-specific E3 ligases atrogin-1 and MuRF1, degradation of myosin heavy chain, and atrophy of myotubes. Inhibition of p38 MAPK by SB203580 abolished acrolein-induced muscle catabolism. Our findings demonstrate that acrolein but not acetaldehyde activates a signaling cascade resulting in muscle catabolism in skeletal myotubes. Although within the limitations of an in vitro study, these findings indicate that acrolein may promote muscle wasting in conditions of increased exposure to this aldehyde.
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Rom
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Kaisari
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel; Orthodontic and Craniofacial Department, Rambam Health Care Campus, Bat Galim, Haifa 31096, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Aizenbud
authors.affiliation: Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel. Electronic address: reznick@tx.technion.ac.il.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Reznick
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000171:Acrolein; D000079:Acetaldehyde
keywords: Acetaldehyde; Acrolein; CS; E3 ubiquitin ligases; Free radicals; GAPDH; GSH; MAPK; MuRF1; Muscle catabolism; MyHC; N-acetylcysteine; NAC; Oxidative stress; RNS; ROS; atrogin-1; cigarette smoke; glyceraldehyde-3-phosphate dehydrogenase; mitogen-activated protein kinase; muscle atrophy F-box protein; muscle ring finger-1 protein; myosin heavy chain; p38 MAPK; reactive nitrogen species; reactive oxygen species; reduced glutathione