Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells.
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.
Ito
Hidenori
H
Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan. itohide@inst-hsc.jp
Ueda
Hiroshi
H
Iwamoto
Ikuko
I
Inaguma
Yutaka
Y
Takizawa
Takenori
T
Asano
Tomiko
T
Kato
Kanefusa
K
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
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