
JOURNALS . PHYSIOLOGY . ORG {
}
Title:
NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubes | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology | American Physiological Society
Description:
Nuclear factor-κB (NF-κB) regulates the transcription of a variety of genes involved in immune responses, cell growth, and cell death. However, the role of NF-κB in muscle biology is poorly understood. We recently reported that tumor necrosis factor-α (TNF-α) rapidly activates NF-κB in differentiated skeletal muscle myotubes and that TNF-α acts directly on the muscle cell to induce protein degradation. In the present study, we ask whether NF-κB mediates the protein loss induced by TNF-α. 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-κBα proteins that are insensitive to degradation via the ubiquitin-proteasome pathway. These mutant proteins selectively inhibit NF-κB 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-α. In contrast, total protein and fast-type myosin heavy-chain levels were unaltered by TNF-α in the transdominant negative cell lines. TNF-α did not induce apoptosis in any cell line, as assessed by DNA ladder and annexin V assays. These data indicate that NF-κB is an essential mediator of TNF-α-induced catabolism in differentiated muscle cells.
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Keywords {🔍}
tnfα, nfκb, myotubes, muscle, protein, cell, differentiated, cells, iκbα, mhcf, loss, activation, iκbαδn, negative, control, american, transfected, levels, apoptosis, data, journal, physiology, skeletal, transdominant, dna, ngml, vector, overexpressed, degradation, mutant, pcmv, fig, content, present, tnfαinduced, wasting, studies, effects, ser, induce, empty, total, inflammatory, nuclear, death, lines, myoblasts, proteins, pathway, cytokine,
Topics {✒️}
r1165 sections pdf nf-κb-binding dna probe overexpressed i-κbαs32/36a exhibited tnf-α-induced muscle wasting tnf-α-induced protein loss i-κbαs32/36a inhibited activation american physiological society tnf-α/nf-κb signaling tnf-α activated nf-κb inhibit nf-κb activation rapidly activates nf-κb mouse recombinant tnf-α jun-nh2-terminal kinases tumor necrosis factor-α tnf-α-induced catabolism dna-binding proteins p50 tnf-α stimulation increases higher tnf-α concentrations inhibits nuclear factor-κb tnf-α-receptor complex activated nf-κb dimer physiological genomics journal western blot analysis fibroblast-derived l929 cells journals quick search protein assay kit mutant i-κbα proteins test nf-κb mediation nf-κb requires phosphorylation activate nf-κb directly determining nf-κb effects download figuredownload powerpoint tnf-α acts directly tnf-α stimulates apoptosis aps website aps member tnf-α-induced apoptosis tnf-α induced apoptosis mutant i-κbα protein inhibitory protein i-κbα circulating tnf-α levels time-matched control myotubes tnf-α signal dna ladder detection evaluate tnf-α effects transdominant negative mutant applied physiology journal nf-κb mediates metabolism american journal annexin v-fitc
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