title: Protective effect of melatonin on TNF-α-induced muscle atrophy in L6 myotubes.
abstract: Muscle atrophy, characterized by decreased cell number and size, is a serious concern for patients afflicted with inflammatory diseases. Mounting evidence indicates that tumor necrosis factor alpha (TNF-α) plays a critical role in muscle atrophy in a number of clinical settings. We hypothesize that reactive oxygen species (ROS) mediate TNF-α-induced muscle cell death and hypotrophy. Recently, melatonin has attracted attention because of its free-radical scavenging and antioxidant properties. The aim of the current study was to evaluate the possible protective role of melatonin in TNF-α-induced muscle cell death and hypotrophy in rat L6 myotubes. To examine this possible role, L6 myotubes were exposed to various concentrations of recombinant TNF-α for 24 hr. We found that TNF-α at a concentration of 100 ng/mL induced ROS generation and decreased cell viability. Further analysis revealed that apoptosis, but not autophagy, may be important for TNF-α-induced cell death. Melatonin significantly attenuated TNF-α-induced ROS generation and apoptosis. In addition, decreased muscle fiber diameter and increased muscle cell proteolysis by TNF-α was highly attenuated by treatment with melatonin. The effects of melatonin were mediated neither through its plasmalemmal receptors nor by modulating the nuclear factor kappa B pathway activated by TNF-α. Taken together, these results suggest that TNF-α may mediate ROS-induced muscle cell death and hypotrophy and that melatonin may be a useful tool for protecting against muscle atrophy stemming from inflammatory diseases.
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Chung
authors.forename: Hae-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
authors.forename: Jung-Geun
authors.initials: JG
authors.lastname: Lim
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D008550:Melatonin / Q000494:pharmacology*; D009133:Muscular Atrophy / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008550:Melatonin
keywords: L6 myotube; TNF‐α; antioxidant enzyme activity; melatonin; muscle atrophy; muscle cell death; reactive oxygen species