Inhibition of mitochondrial protein synthesis impaired C2C12 myoblast differentiation.
Various factors are required for the regulation of muscle cell differentiation. In an attempt to elucidate the mechanism underlying myogenesis, we examined the possible contribution of mitochondria to terminal differentiation of murine myoblast cell line, C2C12, using a specific inhibitor for mitochondrial protein synthesis, tetracycline. Tetracycline impaired myotube formation and induction of muscle creatine kinase activity which was specifically observed in differentiated myocytes. Transcript levels of muscle-specific proteins, creatine kinase and troponin-I were also significantly suppressed in a dose-dependent manner. However, those proteins with myogenic regulatory factors, MyoD and myogenin, and common proteins including glycolytic enzymes were not affected. Cellular viability, mitochondrial transcription, and mitochondrial proliferation were confirmed not to be impaired by tetracycline treatment. These results suggest that mitochondrial stress may affect regulation of differentiation-specific gene expression. This system may contribute to an understanding of mechanisms for differentiation inhibition caused by inhibitors of mitochondrial protein synthesis that have also been observed in other kinds of cells.
Hamai
N
N
Division of Physiology, Osaka University, Japan.
Nakamura
M
M
Asano
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003402:Creatine Kinase / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics; D018008:Myogenin / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013752:Tetracycline / Q000494:pharmacology; D019210:Troponin I / Q000096:biosynthesis / Q000235:genetics
D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D019210:Troponin I; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D013752:Tetracycline