NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.
MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.
Guttridge
D C
DC
Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, Department of Biology, University of North Carolina, Chapel Hill, Mason Farm Road, Campus Box 7295, Chapel Hill, NC, 27599-7295, USA.
Mayo
M W
MW
Madrid
L V
LV
Wang
C Y
CY
Baldwin
A S
AS
D000818:Animals; D016466:CHO Cells; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020672:I-kappa B Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007378:Interleukins; D017570:MyoD Protein; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D007371:Interferon-gamma