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Science 29 September 2000:
Vol. 289. no. 5488, pp. 2363 - 2366
DOI: 10.1126/science.289.5488.2363
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Reports

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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Molecular-Based Therapeutic Approaches in Treatment of Anorexia of Aging and Cancer Cachexia.
D. Hamerman (2002)
J. Gerontol. A Biol. Sci. Med. Sci. 57, M511-518
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Myotrophin/V-1, a Protein Up-regulated in the Failing Human Heart and in Postnatal Cerebellum, Converts NFkappa B p50-p65 Heterodimers to p50-p50 and p65-p65 Homodimers.
P. Knuefermann, P. Chen, A. Misra, S.-P. Shi, M. Abdellatif, and N. Sivasubramanian (2002)
J. Biol. Chem. 277, 23888-23897
   Abstract »    Full Text »    PDF »
Identification of NF-{kappa}B-Dependent Gene Networks in Respiratory Syncytial Virus-Infected Cells.
B. Tian, Y. Zhang, B. A. Luxon, R. P. Garofalo, A. Casola, M. Sinha, and A. R. Brasier (2002)
J. Virol. 76, 6800-6814
   Abstract »    Full Text »    PDF »
Proinflammatory and Th1 Cytokine Alterations following Ultraviolet Radiation Enhancement of Disease Due to Influenza Infection in Mice.
L. K. Ryan, L. R. Copeland, M. J. Daniels, E. R. Costa, and M. J. K. Selgrade (2002)
Toxicol. Sci. 67, 88-97
   Abstract »    Full Text »    PDF »
Systemic Effects in COPD*.
E. F. M. Wouters, E. C. Creutzberg, and A. M. W. J. Schols (2002)
Chest 121 , 127S-130S
   Abstract »    Full Text »    PDF »
Lethal Weight Loss: The Focus Shifts to Signal Transduction.
K. J. Tracey (2002)
Sci. STKE 2002, pe21
   Abstract »    Full Text »    PDF »
Activation of an alternative NF-{kappa}B pathway in skeletal muscle during disuse atrophy.
R. B. HUNTER, E. J. STEVENSON, A. KONCAREVIC, H. MITCHELL-FELTON, D. A. ESSIG, and S. C. KANDARIAN (2002)
FASEB J 16, 529-538
   Abstract »    Full Text »    PDF »
p65-NF{kappa}B synergizes with Notch to activate transcription by triggering cytoplasmic translocation of the nuclear receptor corepressor N-CoR.
L. Espinosa, S. Santos, J. Ingles-Esteve, P. Munoz-Canoves, and A. Bigas (2002)
J. Cell Sci. 115, 1295-1303
   Abstract »    Full Text »    PDF »
Cancer Anorexia-Cachexia Syndrome: Current Issues in Research and Management.
A. Inui (2002)
CA Cancer J Clin 52, 72-91
   Abstract »    Full Text »    PDF »
Potentiation of Tumor Necrosis Factor-mediated Apoptosis of Oral Squamous Cell Carcinoma Cells by Adenovirus-mediated Gene Transfer of NF-{kappa}B Inhibitor.
S. Chen, A. Fribley, and C.-Y. Wang (2002)
Journal of Dental Research 81, 98-102
   Abstract »    Full Text »    PDF »
Peripheral Muscle Wasting in Chronic Obstructive Pulmonary Disease . Clinical Relevance and Mechanisms.
R. DEBIGARE, C. H. COTE, and F. MALTAIS (2001)
Am. J. Respir. Crit. Care Med. 164, 1712-1717
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