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.

[1]  R. Cooper,et al.  In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle. , 1999, Journal of cell science.

[2]  Chris Albanese,et al.  NF-κB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1 , 1999, Molecular and Cellular Biology.

[3]  J. Beckmann,et al.  Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IκBα/NF-κB pathway in limb-girdle muscular dystrophy type 2A , 1999, Nature Medicine.

[4]  F. López‐Soriano,et al.  The role of cytokines in cancer cachexia , 1999, Medicinal research reviews.

[5]  M. Tisdale.  Biology of cachexia. , 1997, Journal of the National Cancer Institute.

[6]  E. Duda,et al.  TNF inhibits myogenesis and downregulates the expression of myogenic regulatory factors myoD and myogenin. , 1997, European journal of cell biology.

[7]  P. Silver,et al.  MyoD is required for myogenic stem cell function in adult skeletal muscle. , 1996, Genes & development.

[8]  M. Zhang,et al.  MyoD protein accumulates in satellite cells and is neurally regulated in regenerating myotubes and skeletal muscle fibers , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[9]  T. Maniatis,et al.  NF-κB: A lesson in family values , 1995, Cell.

[10]  A. Lassar,et al.  Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. , 1994, Current opinion in cell biology.

[11]  M. Rudnicki,et al.  Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development , 1992, Cell.

[12]  A. Oliff,et al.  Tumors secreting human TNF/cachectin induce cachexia in mice , 1987, Cell.

[13]  T. Ogihara,et al.  Intratumoral injection of oligonucleotides to the NFκB binding site inhibits cachexia in a mouse tumor model , 1999, Gene Therapy.

[14]  B. Black,et al.  Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. , 1998, Annual review of cell and developmental biology.

[15]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[16]  A. Baldwin,et al.  THE NF-κB AND IκB PROTEINS: New Discoveries and Insights , 1996 .

[17]  K. Tracey,et al.  Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. , 1994, Annual review of medicine.

[18]  J. Eys.  Nutrition and cancer: physiological interrelationships. , 1985, Annual review of nutrition.