Tumor necrosis factor-α exerts pro-myogenic action in C2C12 myoblasts dvia sphingosine kinase/S1P2 signaling

In this study, we report that low doses of tumor necrosis factor-alpha (TNF alpha) promote myogenesis in C2C12 myoblasts. Moreover, the cytokine increased sphingosine kinase (SphK) activity and induced SphK1 translocation to membranes. The inhibition of SphK functionality by various approaches abrogated the pro-myogenic effect of TNFa. Moreover, silencing of S1P(2) impaired the positive action of TIN Fa on myogenesis. These results represent the first evidence that SphK/S1P(2) axis is required for the regulation of myogenesis by TNFa. In view of the physiological role of TNF alpha in muscle regeneration, the present finding reinforces the notion that SphK/SIP2 signaling is critically implicated in myogenesis. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.