Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways

R.C.J. Langen, A.M.W.J. Schols, M.C.J.M. Kelders, A.L.J. van der Velden, E.F.M. Wouters, Y.M.W. Janssen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways.

Langen RC, Schols AM, Kelders MC, Van Der Velden JL, Wouters EF, Janssen-Heininger YM.

Department of Pulmonology, Maastricht University, The Netherlands.

Muscle wasting accompanies diseases that are associated with chronic elevated levels of circulating inflammatory cytokines and oxidative stress. We previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) inhibits myogenic differentiation via the activation of nuclear factor-kappaB (NF-kappaB). The goal of the present study was to determine whether this process depends on the induction of oxidative stress. We demonstrate here that TNF-alpha causes a decrease in reduced glutathione (GSH) during myogenic differentiation of C(2)C(12) cells, which coincides with an elevated generation of reactive oxygen species. Supplementation of cellular GSH with N-acetyl-l-cysteine (NAC) did not reverse the inhibitory effects of TNF-alpha on troponin I promoter activation and only partially restored creatine kinase activity in TNF-alpha-treated cells. In contrast, the administration of NAC before treatment with TNF-alpha almost completely restored the formation of multinucleated myotubes. NAC decreased TNF-alpha-induced activation of NF-kappaB only marginally, indicating that the redox-sensitive component of the inhibition of myogenic differentiation by TNF-alpha occurred independently, or downstream of NF-kappaB. Our observations suggest that the inhibitory effects of TNF-alpha on myogenesis can be uncoupled in a redox-sensitive component affecting myotube formation and a redox independent component affecting myogenic protein expression.

Original languageEnglish
Pages (from-to)714-721
Number of pages8
JournalAmerican Journal of Physiology-Cell Physiology
Issue number3
Publication statusPublished - 1 Jan 2002


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