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

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DOI: 10.4236/ajmb.2011.11002    4,788 Downloads   10,207 Views   Citations

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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Sakuma, K. and Yamaguchi, A. (2011) Cyclosporin A inhibits the growth of neonatal MHC-expressing myotubes independent of NFATc1 and NFATc3 in the mechanically overloaded soleus muscle of mice. American Journal of Molecular Biology, 1, 7-16. doi: 10.4236/ajmb.2011.11002.

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