Differential responses to oxidative stress and calcium influx on expression of the transforming growth factor-beta family in myoblasts and myotubes.
Changes in gene expression of TGF-beta 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-beta family was modulated in response to H(2)O(2) and A23187. Treatment with H(2)O(2) decreased expression of TGF-beta3, BMP-4, ALK4, ALK5, and ActRIIB, and increased expression of inhibin alpha and inhibin betaA 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-beta1, TGF-beta2, inhibin alpha, inhibin betaA, ALK2, and ALK3 expression. These results indicate that oxidative stress and Ca(2+) influx affect expression of the TGF-beta family in C2C12 myoblasts and myotubes.
Furutani
Yuuma
Y
Division of Applied Biosciences, Kyoto University Graduate School of Agriculture, Kyoto, Japan.
Murakami
Masaru
M
Funaba
Masayuki
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D005810:Multigene Family / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D055411:TGF-beta Superfamily Proteins / Q000235:genetics* / Q000378:metabolism
D055411:TGF-beta Superfamily Proteins; D006861:Hydrogen Peroxide; D002118:Calcium