title: Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells.
abstract: Addition of nordihydroguaiaretic acid (NDGA) to the differentiation medium of C2C12 mouse myoblast cells caused severe inhibition of the formation of myotubes and suppressed differentiation-dependent elevation in the levels of the creatine kinase M isozyme (CKM). Under these conditions, NDGA did not cause significant increase of damaged cells, as detected by annexin-V-FITC assay, or induction of heat shock proteins, known to be a response against extracellular stress. The results suggest that NDGA itself is not toxic but can effectively blocks the differentiation-dependent increase of CKM during C2C12 differentiation. The levels of muscle specific bHLH proteins MyoD, Myf5, and myogenin were also decreased by addition of NDGA, indicating a block of the initial step of the myogenesis through downregulation of muscle specific genes. NDGA is known to be a lipoxygenase inhibitor but other examples, like MK-886 and CDC, did not exert the same effects on differentiation of muscle cells, indicating that mechanisms of NDGA action are independent of its influence on lipoxygenase.
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan. itohide@inst-hsc.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Inaguma
authors.forename: Takenori
authors.initials: T
authors.lastname: Takizawa
authors.forename: Tomiko
authors.initials: T
authors.lastname: Asano
authors.forename: Kanefusa
authors.initials: K
authors.lastname: Kato
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D007527:Isoenzymes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology*; D051379:Mice; D024510:Muscle Development / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D015534:Trans-Activators; D009637:Masoprocol; D003402:Creatine Kinase