title: Direct effects of tumor necrosis factor alpha (TNF-alpha) on L6 myotubes.
abstract: Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine responsible for a diverse range of signaling events within cells. We studied direct effects of TNF-alpha on skeletal muscle protein content. Incubation of the L6 myotubes with 1 to 10 U/ml of TNF-alpha resulted in a significant increase of total and myofibrillar protein contents as compared with the control. However, incubation with lower (0.001-0.1 U/ ml) or higher (100-300 U/ml) doses of TNF-alpha resulted in a decrease of protein content. These findings suggest that TNF-alpha may elicit both anabolic and catabolic effects on L6 myotubes in a dose dependent manner. The anabolic effect of TNF-alpha was mediated at least in part by mitogen activated protein kinase (MAPK), especially by an extracellular-regulated kinases (ERK). This divergent effect of TNF-alpha may be crucial to elucidate the complexity of TNF-alpha action on the skeletal muscle.
authors.affiliation: Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine.
authors.forename: Enas Atef
authors.initials: EA
authors.lastname: el-Naggar
authors.forename: Fumio
authors.initials: F
authors.lastname: Kanda
authors.forename: Shiho
authors.initials: S
authors.lastname: Okuda
authors.forename: Nobuya
authors.initials: N
authors.lastname: Maeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nishimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishihara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
mesh_terms: D045930:Anabolic Agents; D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007700:Kinetics; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000187:drug effects*; D009124:Muscle Proteins / Q000032:analysis*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009210:Myofibrils / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D045930:Anabolic Agents; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases