Heat shock protects L6 myotubes from catabolic effects of dexamethasone and prevents downregulation of NF-kappaB.
Glucocorticoids are the most important mediator of muscle cachexia in various catabolic conditions. Recent studies suggest that the transcription factor NF-kappaB acts as a suppressor of genes in the ubiquitin-proteasome proteolytic pathway and that glucocorticoids increase muscle proteolysis by downregulating NF-kappaB activity. The heat shock (stress) response, characterized by the induction of heat shock proteins, confers a protective effect against a variety of harmful stimuli. In the present study, we tested the hypothesis that the heat shock response protects muscle cells from the catabolic effects of dexamethasone and prevents downregulation of NF-kappaB. Cultured L6 myotubes were subjected to heat shock (43 degrees C for 1 h) followed by recovery at 37 degrees C for 1 h. Thereafter, cells were treated for 6 h with 1 microM dexamethasone, during which period protein degradation was measured as release of TCA-soluble radioactivity from proteins that had been prelabeled with [(3)H]tyrosine. Heat shock resulted in increased protein and mRNA levels for heat shock protein 70. The increase in protein degradation induced by dexamethasone was prevented in cells expressing the heat shock response. In the same cells, dexamethasone-induced downregulation of NF-kappaB DNA binding activity was blocked. The present results suggest that the heat shock response may protect muscle cells from the catabolic effects of dexamethasone and that this effect of heat shock may be related to inhibited downregulation of NF-kappaB activity.
Luo
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Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA.
Sun
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Hungness
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Hasselgren
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D000818:Animals; D002100:Cachexia / Q000378:metabolism / Q000517:prevention & control; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013696:Temperature
D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D003907:Dexamethasone