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

• Published in: Science (American Association for the Advancement of Science) Vol. 289; no. 5488; pp. 2363 - 2366
• Main Authors: Guttridge, Denis C., Mayo, Marty W., Madrid, Lee V., Wang, Cun-Yu, Baldwin, Albert S.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 29-09-2000; American Association for the Advancement of Science
• Subjects: Age; Atrophy, Muscular; Biological and medical sciences; Cachexia; Cell physiology; Cytokines; Fundamental and applied biological sciences. Psychology; Messenger RNA; Molecular and cellular biology; Mortality; Muscle fibers; Muscles; MyoD protein; Plasmids; Signal transduction; Skeletal muscle; Tumor necrosis factors; Cytokine; Rodentia; Cachexia; Cell differentiation; Gene expression; Myogenic factor; Signal transduction; Vertebrata; Regulation(control); Mammalia; Messenger RNA; Mouse; Tumor necrosis factor; Muscle; Lesion; Transcription factor NFκB; Transcription factor; Repair; Transcription factor MyoD; Gamma interferon
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.289.5488.2363

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-κB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-κB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-κB inhibited SMD by suppressing MyoD mRNA at the post-transcriptional level. In contrast, in differentiated myotubes, TNF plus interferon-γ (IFN-γ) signaling was required for NF-κB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-γ expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.