Differential responses to oxidative stress and calcium influx on expression of the transforming growth factor- β family in myoblasts and myotubes.

Changes in gene expression of TGF- β family members and their receptors in response to treatment with H2O2 and a calcium ionophore, A23187, were examined in C2C12 myoblasts and myotubes. The expression of Myf5, an initial regulator of myogenesis, was increased by A23187, and H2O2 inhibited the up-regulation of Myf5. Treatment with H2O2 decreased the expression of MHC IIb, a protein component of the myofibrils, irrespective of the presence of A23187, suggesting an inhibitory role of oxidative stress for myogenesis. Expression of ligands and receptors for the TGF- β family was modulated in response to H2O2 and A23187. Treatment with H2O2 decreased expression of TGF-β3, BMP-4, ALK4, ALK5, and ActRIIB, and increased expression of inhibin α and inhibin βA in either the myoblast stage or the myotube stage, or both. A23187 potentiated down-regulation of BMP-4 and ALK4 expression, and up-regulation of TGF-β1, TGF-β2, inhibin α, inhibin βA, ALK2, and ALK3 expression. These results indicate that oxidative stress and Ca2+ influx affect expression of the TGF- β family in C2C12 myoblasts and myotubes. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]