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 H 2 O 2 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 H 2 O 2 inhibited the up‐regulation of Myf5 . Treatment with H 2 O 2 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 H 2 O 2 and A23187. Treatment with H 2 O 2 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 Ca 2+ influx affect expression of the TGF‐ β family in C2C12 myoblasts and myotubes. Copyright © 2009 John Wiley & Sons, Ltd.