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Science 289 (5488): 2363-2366

Copyright © 2000 by the American Association for the Advancement of Science

NF-kappa B-Induced Loss of MyoD Messenger RNA: Possible Role in Muscle Decay and Cachexia

Denis C. Guttridge,1 Marty W. Mayo,1 Lee V. Madrid,12 Cun-Yu Wang,1* Albert S. Baldwin Jr.123dagger

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappa B) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappa B in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappa B 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-kappa B-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.

1 Lineberger Comprehensive Cancer Center,
2 Curriculum in Genetics and Molecular Biology,
3 Department of Biology, University of North Carolina, Chapel Hill, Mason Farm Road, Campus Box 7295, Chapel Hill, NC, 27599-7295, USA.
*   Present address: Laboratory of Molecular Signaling, Department of Biologic and Material Science, University of Michigan, Ann Arbor, MI 48109, USA.

dagger    To whom correspondence should be addressed. E-mail: jhall{at}med.unc.edu

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J. Huang, L. Teng, L. Li, T. Liu, L. Li, D. Chen, L.-G. Xu, Z. Zhai, and H.-B. Shu (2004)
J. Biol. Chem. 279, 16847-16853
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Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4.
S. Bozinovski, J. Jones, S.-J. Beavitt, A. D. Cook, J. A. Hamilton, and G. P. Anderson (2004)
Am J Physiol Lung Cell Mol Physiol 286, L877-L885
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Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization.
R. C. J. LANGEN, J. L. J. VAN DER VELDEN, A. M. W. J. SCHOLS, M. C. J. M. KELDERS, E. F. M. WOUTERS, and Y. M. W. JANSSEN-HEININGER (2004)
FASEB J 18, 227-237
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RNAi-mediated HuR Depletion Leads to the Inhibition of Muscle Cell Differentiation.
K. van der Giessen, S. Di-Marco, E. Clair, and I. E. Gallouzi (2003)
J. Biol. Chem. 278, 47119-47128
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Oxidant metabolism in chronic obstructive pulmonary disease.
A.W. Boots, G.R.M.M. Haenen, and A. Bast (2003)
Eur. Respir. J. 22, 14s-27s
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Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease.
R.T. Jagoe and M.P.K.J. Engelen (2003)
Eur. Respir. J. 22, 52s-63s
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Nuclear Factor-{kappa}B Activation in Endothelium by Chlamydia pneumoniae without Active Infection.
J. T. Baer, T. V. du Laney, P. B. Wyrick, A. S. McCain, T. A. Fischer, E. P. Merricks, A. S. Baldwin, and T. C. Nichols (2003)
The Journal of Infectious Disease 188, 1094-1097
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NF-{kappa}B mediates inhibition of mesenchymal cell differentiation through a posttranscriptional gene silencing mechanism.
R. Sitcheran, P. C. Cogswell, and A. S. Baldwin Jr. (2003)
Genes & Dev. 17, 2368-2373
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Review Article: Exercise, Aging, and Muscle Protein Metabolism.
K. E. Yarasheski (2003)
J Gerontol A Biol Sci Med Sci 58, M918-M922
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Cytokine-induced Patterns of Gene Expression in Skeletal Muscle Tissue.
T. Alon, J. M. Friedman, and N. D. Socci (2003)
J. Biol. Chem. 278, 32324-32334
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