期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 279, 期 4, 页码 R1165-R1170出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.2000.279.4.R1165
关键词
cachexia; cytokine; free radicals; signal transduction; inflammation
类别
资金
- NHLBI NIH HHS [HL-59878] Funding Source: Medline
Nuclear factor-kappa B (NF kappa B) regulates the transcription of a variety of genes involved in immune responses, cell growth, and cell death. However, the role of NF-kappa B in muscle biology is poorly understood. We recently reported that tumor necrosis factor-alpha (TNF-alpha) rapidly activates NF-kappa B in differentiated skeletal muscle myotubes and that TNF-alpha acts directly on the muscle cell to induce protein degradation. In the present study, we ask whether NF-kappa B mediates the protein loss induced by TNF-alpha. We addressed this problem by creating stable, transdominant negative muscle cell lines. C2C12 myoblasts were transfected with viral plasmid constructs that induce overexpression of mutant I-kappa B alpha proteins that are insensitive to degradation via the ubiquitin-proteasome pathway. These mutant proteins selectively inhibit NF-kappa B activation. We found that differentiated myotubes transfected with the empty viral vector (controls) underwent a drop in total protein content and in fast-type myosin heavy-chain content during 72 h of exposure to TNF-alpha. In contrast, total protein and fast-type myosin heavy-chain levels were unaltered by TNF-alpha in the transdominant negative cell lines. TNF-alpha did not induce apoptosis in any cell line, as assessed by DNA ladder and annexin V assays. These data indicate that NF-kappa B is an essential mediator of TNF-alpha-induced catabolism in differentiated muscle cells.
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