Document Detail

Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways.
MedLine Citation:
PMID:  12176728     Owner:  NLM     Status:  MEDLINE    
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.
Ramon C J Langen; Annemie M W J Schols; Marco C J M Kelders; Jos L J Van Der Velden; Emiel F M Wouters; Yvonne M W Janssen-Heininger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  283     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-14     Completed Date:  2002-09-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C714-21     Citation Subset:  IM    
Department of Pulmonology, Maastricht University, The Netherlands.
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MeSH Terms
Acetylcysteine / pharmacology
Antioxidants / pharmacology
Cell Differentiation / drug effects*
Cell Line
Creatine Kinase / metabolism
Enzyme Activation / drug effects
Glutathione / metabolism
Muscle Development / drug effects*
Muscle, Skeletal / cytology,  drug effects*,  metabolism
NF-kappa B / metabolism
Oxidation-Reduction / drug effects
Oxidative Stress / drug effects,  physiology
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*,  physiology
Tumor Necrosis Factor-alpha / pharmacology*
Reg. No./Substance:
0/Antioxidants; 0/NF-kappa B; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; EC Kinase

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