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Chin, E.R., Olson, E.N., Richardson, J.A., Yang, Q., Humphries, C., Shelton, J.M., Wu, H., Zhu, W., Bassel-Duby, R. and Williams, R.S. (1998) A calcineurin- dependent transcriptional pathway controls skeletal muscle fiber type. Genes and Development, 12, 2499-2509. doi:10.1101/gad.12.16.2499

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• TITLE: Cyclosporin A inhibits the growth of neonatal MHC-expressing myotubes independent of NFATc1 and NFATc3 in the mechanically overloaded soleus muscle of mice

  AUTHORS: Kunihiro Sakuma, Akihiko Yamaguchi

  KEYWORDS: Calcineurin; Nfatc3; Neonatal MHC; Skeletal Muscle; Hypertrophy

  JOURNAL NAME: American Journal of Molecular Biology, Vol.1 No.1, April 21, 2011

  ABSTRACT: ABSTRACT The molecular signaling pathway linked to hyper-trophy of the anti-gravity/postural soleus muscle af-ter mechanical overloading has not been identified. Using Western blot and immunohistochemical analy-ses, we investigated whether the amounts of NFATc3, GSK-3?, NFATc1, and neonatal MHC change in the mechanically overloaded soleus muscle after cyc-losporine A (CsA) treatment. Adult male ICR mice were subjected to a surgical ablation of the gas-trocnemius muscle and treated with either CsA (25 mg/Kg) or vehicle once daily. They were sacrificed at 2, 4, 7, 10, and 14 days post-injury. Mechanical over-loading resulted in a significant increase in the wet weight and the cross-sectional area of slow and fast fibers of the soleus muscle in placebo-treated mice but not CsA-treated mice. After 4 days of mechanical overloading, we observed a similar co-localization of neonatal MHC and NFATc3 in several myotubes of both mice. The placebo-treated mice possessed larger myotubes with neonatal MHC than CsA-treated mice. At 7 days, mechanical overloading induced marked expression of neonatal MHC in myotubes and/or myofibers. Such neonatal MHC-positive fibers emerged less often in the hypertrophied soleus mus-cle subjected to treatment with CsA. CsA treatment did not significantly change the amount of GSK-3? protein in the soleus muscle. The modulation of growth in neonatal MHC-positive myofibers by CsA treatment may inhibit the hypertrophic process in the soleus muscle after mechanical overloading.