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Simvastatin suppresses the differentiation of C2C12 myoblast cells via a Rac pathway

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Abstract

Statins, which are known as cholesterol-lowering drugs, have several additional effects including the enhancement of bone formation and the stimulation of smooth muscle cell proliferation. In this study, we investigated the signal pathway of simvastatin operating in C2C12 myoblast cells. Myotube formation of C2C12 cells was efficiently blocked by 1 μM simvastatin, and mevalonic acid was able to cancel this effect. Geranylgeranyl pyrophosphate restored the myotube formation, whereas farnesyl pyrophosphate did not. These findings demonstrate that the Rho family, such as Rho, Rac and Cdc42, occurring downstream of geranylgeranyl pyrophosphate in the mevalonic acid pathway, was involved in the simvastatin-mediated blockage of myotube formation. An inhibitor of Rho kinase did not influence the myotube formation; whereas an inhibitor of Rac blocked this process. Taken together, we conclude that the differentiation of C2C12 cells into myotubes was blocked by simvastatin through the pathway mediated by Rac, not by Rho.

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Authors and Affiliations

  1. Department of Oral Molecular Biology, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan

    Tomomi T. Baba & Takayuki K. Nemoto

  2. Department of Cell Biology, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan

    Toshihiro Miyazaki

  3. Department of Oral Biochemistry, School of Dentistry, Tsurumi University, Yokohama, 230-8501, Japan

    Shinichiro Oida

Authors
  1. Tomomi T. Baba
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  2. Takayuki K. Nemoto
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  3. Toshihiro Miyazaki
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  4. Shinichiro Oida
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Correspondence to Tomomi T. Baba.

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Baba, T.T., Nemoto, T.K., Miyazaki, T. et al. Simvastatin suppresses the differentiation of C2C12 myoblast cells via a Rac pathway. J Muscle Res Cell Motil 29, 127–134 (2008). https://doi.org/10.1007/s10974-008-9146-9

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  • DOI: https://doi.org/10.1007/s10974-008-9146-9

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