Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells
Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells
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DOI：
10.1002/jcp.20177
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发表时间：
2005-03-01
影响因子：
5.6
通讯作者：
Kato, K
中科院分区：
文献类型：
--
作者：
Ito, H;Ueda, H;Kato, K
此外，去甲二氢愈创木酸（NDGA）的分化培养基中的C2 C12小鼠成肌细胞引起严重的抑制肌管的形成和抑制分化依赖性升高的肌酸激酶M同工酶（CKM）的水平。在这些条件下，NDGA没有引起损伤细胞的显著增加，如通过膜联蛋白-V-FITC测定所检测到的，或热休克蛋白的诱导，已知热休克蛋白是对细胞外应激的反应。结果表明，NDGA本身没有毒性，但可以有效地阻断C2 C12分化过程中CKM的分化依赖性增加。肌肉特异性bHLH蛋白MyoD、Myf 5和肌细胞生成素的水平也通过添加NDGA而降低，表明通过下调肌肉特异性基因阻断了肌细胞生成的初始步骤。已知NDGA是一种脂氧合酶抑制剂，但其他例子，如MK-886和CDC，对肌肉细胞的分化没有发挥相同的作用，这表明NDGA的作用机制与其对脂氧合酶的影响无关。(C)2004 Wiley-Liss，Inc.
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. (C) 2004 Wiley-Liss, Inc.