Tumor necrosis factor-alpha exerts pro-myogenic action in C2C12 myoblasts via sphingosine kinase/S1P2 signaling.
In this study, we report that low doses of tumor necrosis factor-alpha (TNFalpha) 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 TNFalpha. Moreover, silencing of S1P(2) impaired the positive action of TNFalpha on myogenesis. These results represent the first evidence that SphK/S1P(2) axis is required for the regulation of myogenesis by TNFalpha. In view of the physiological role of TNFalpha in muscle regeneration, the present finding reinforces the notion that SphK/S1P(2) signaling is critically implicated in myogenesis.
Donati
Chiara
C
Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Viale G.B. Morgagni 50, 50134 Firenze, Italy.
Nincheri
Paola
P
Cencetti
Francesca
F
Rapizzi
Elena
E
Farnararo
Marta
M
Bruni
Paola
P
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000099157:Sphingosine Kinase
D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000099157:Sphingosine Kinase