Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors
Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors
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DOI：
10.1074/jbc.275.4.2733
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发表时间：
2000-01-28
影响因子：
4.8
通讯作者：
Cabello, G
中科院分区：
文献类型：
--
作者：
Rochard, P;Rodier, A;Cabello, G
为了表征与线粒体活性受损抑制细胞分化有关的调节途径，我研究了使用鸟类成肌细胞细胞系（QM7）研究细胞器活性与肌发生之间的关系。氯霉素对线粒体翻译的抑制导致肌细胞分化的有效块，羰基氰化物P-（三氟甲氧基）苯基氢化唑酮和寡霉素，从而在不同的水平上影响细胞器，从而施加了相似的影响。此外，我们提供了证据，表明这种现象不是细胞生存力改变的结果。相反，线粒体T3受体（p43）的过表达刺激了细胞器活性，并强烈增强了成肌细胞分化。结果表明，与CMD1（Chiche Chiche Myod）和MyF5相比，线粒体活性参与了肌发生的实际调节，进一步支持了肌肉调节性基因肌生成素。尽管肌蛋白蛋白mRNA和蛋白质水平通过氯霉素治疗下调，但它们被p43的过表达上调，与转基因的表达水平保持正相关，但我们还发现，肌蛋白或CMD1过表达在氯霉素培养的肌细胞中没有是恢复分化，从而表明线粒体活性的改变会干扰肌源性因子诱导末端分化的能力。
To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, me investigated the relationships occurring between organelle activity and myogenesis using an avian myoblast cell line (QM7). The inhibition of mitochondrial translation by chloramphenicol led to a potent block of myoblast differentiation, Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomycin, which affect the organelle at different levels, exerted a similar influence. In addition, we provided evidence that this phenomenon was not the result of an alteration in cell viability. Conversely, overexpression of the mitochondrial T3 receptor (p43) stimulated organelle activity and strongly potentiated myoblast differentiation. The involvement of mitochondrial activity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast to CMD1 (chicken MyoD) and myf5, is a specific transcriptional target of mitochondrial activity. Whereas myogenin mRNA and protein levels were down-regulated by chloramphenicol treatment, they were up-regulated by p43 overexpression, in a positive relationship with the expression level of the transgene, We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation.