Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-11-7
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1165-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes.
pubmed:affiliation
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.