Source:http://linkedlifedata.com/resource/pubmed/id/11003979
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2000-11-7
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pubmed:abstractText |
Nuclear factor-kappaB (NF-kappaB) regulates the transcription of a variety of genes involved in immune responses, cell growth, and cell death. However, the role of NF-kappaB in muscle biology is poorly understood. We recently reported that tumor necrosis factor-alpha (TNF-alpha) rapidly activates NF-kappaB 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-kappaB 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-kappaBalpha proteins that are insensitive to degradation via the ubiquitin-proteasome pathway. These mutant proteins selectively inhibit NF-kappaB 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-kappaB is an essential mediator of TNF-alpha-induced catabolism in differentiated muscle cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0363-6119
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R1165-70
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11003979-Animals,
pubmed-meshheading:11003979-Cell Differentiation,
pubmed-meshheading:11003979-Cell Line,
pubmed-meshheading:11003979-DNA-Binding Proteins,
pubmed-meshheading:11003979-I-kappa B Proteins,
pubmed-meshheading:11003979-Kinetics,
pubmed-meshheading:11003979-Mice,
pubmed-meshheading:11003979-Muscle, Skeletal,
pubmed-meshheading:11003979-Muscle Proteins,
pubmed-meshheading:11003979-Myosin Heavy Chains,
pubmed-meshheading:11003979-NF-kappa B,
pubmed-meshheading:11003979-Recombinant Proteins,
pubmed-meshheading:11003979-Time Factors,
pubmed-meshheading:11003979-Transfection,
pubmed-meshheading:11003979-Tumor Necrosis Factor-alpha
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pubmed:year |
2000
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pubmed:articleTitle |
NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes.
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pubmed:affiliation |
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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