Cyclosporin-A inhibits stretch-induced changes in myosin heavy chain expression in C2C12 skeletal muscle cells

Studies in vivo, have shown that passive stretch of skeletal muscle induces changes in contractile protein expression. In the present study the effects of passive stretch upon myosin heavy chain (MyHC) expression were examined in C2C12 cell myotubes. Passive stretch induced an upregulation of adult fast and slow MyHCs, which was prevented by cyclosporin A (CsA), an inhibitor of calcineurin. Calcineurin has been shown to act via the dephosphorylation of NFAT and MEF2 transcriptional factors. In this study no significant change in the phosphorylation state of these factors was observed. In contrast stretch induced an alteration in the levels of the myogenic regulatory factors (MRFs) MyoD, myogenin and myf5. The modulation in the level of these MRFs was also inhibited by CsA. These data indicate that changes in muscle phenotype in C2C12 can be modulated by passive stretch and some of these changes are calcineurin dependent. Copyright (c) 2004 John Wiley & Sons, Ltd.