Premium
TNF‐α regulates early differentiation of C2C12 myoblasts in an autocrine fashion
Author(s) -
Li Yi-Ping,
Schwartz Robert J.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0632fje
Subject(s) - c2c12 , autocrine signalling , myocyte , tumor necrosis factor alpha , microbiology and biotechnology , myogenesis , medicine , biology , endocrinology , receptor
Tumor necrosis factor‐α (TNF‐α) has long been known to mediate skeletal muscle protein catabolism as a humoral factor. However, recent findings that muscle normally synthesizes TNF‐α and that strenuous exercise increases circulating TNF‐α in healthy individuals raised the possibility that this cytokine may also have a physiological role in skeletal muscle. In this study, we observed a basal level of TNF‐α expression in C2C12 myoblasts that was markedly up‐regulated by serum restriction. Serum restriction also increased nuclear factor‐κB (NF‐κB) activity, which could be blocked by a TNF‐α‐neutralizing antibody. This antibody also inhibited the expression of a differentiation marker, adult fast myosin heavy chain, during the initial 24 h of serum restriction. Conversely, fast myosin heavy chain expression was stimulated by exogenous TNF‐α during the same time period, which could be blocked by a dominant negative inhibitor of NF‐κB activation. TNF‐α rapidly stimulated the binding activity of serum response factor (SRF), a transcription factor required for myoblast differentiation, and expression of the SRF‐dependent skeletal muscle α‐actin gene. These results demonstrate for the first time that TNF‐α is an endogenous muscle factor that promotes the early phase of differentiation by stimulating NF‐κB and SRF activity.