Heat shock protects L6 myotubes from catabolic effects of dexamethasone and prevents downregulation of NF-kappa B

Glucocorticoids are the most important mediator of muscle cachexia in vario us catabolic conditions. Recent studies suggest that the transcription fact or NF-kappaB acts as a suppressor of genes in the ubiquitin-proteasome prot eolytic pathway and that glucocorticoids increase muscle proteolysis by dow nregulating NF-kappaB activity. The heat shock (stress) response, character ized by the induction of heat shock proteins, confers a protective effect a gainst a variety of harmful stimuli. In the present study, we tested the hy pothesis that the heat shock response protects muscle cells from the catabo lic effects of dexamethasone and prevents downregulation of NF-kappaB. Cult ured L6 myotubes were subjected to heat shock (43 degreesC for 1 h) followe d by recovery at 37 degreesC for 1 h. Thereafter, cells were treated for 6 h with 1 muM dexamethasone, during which period protein degradation was mea sured as release of TCA-soluble radio-activity from proteins that had been prelabeled with [H-3]-tyrosine. Heat shock resulted in increased protein an d mRNA levels for heat shock protein 70. The increase in protein degradatio n induced by dexamethasone was prevented in cells expressing the heat shock response. In the same cells, dexamethasone-induced downregulation of NF-ka ppaB 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 inhibit ed downregulation of NF-kappaB activity.