Activation of HSF and selective increase in heat-shock proteins by acute dexamethasone treatment.
Heat-shock proteins (HSPs) are an important family of endogenous protective proteins, which increase in response to myocardial ischemia and other stresses. Overexpression of HSP72 is cardioprotective. We were interested in the regulation of heat-shock factor (HSF), the transcription factor for HSP genes. Previously we have observed that the inflammatory cytokine tumor necrosis factor-alpha increases HSP72 levels and postulated that dexamethasone might effect the heat shock response. In the adult rat cardiac myocyte we found that treatment with either low (10 microM)- or high (100 microM)-dose dexamethasone activated HSF by 2-6 h as determined by gel shift assay without evidence of cytotoxicity. Although HSF activation is a key step in expression of HSP72, this may not result in an increase in HSP72. We found that 10 microM dexamethasone increased HSP72 38%, and 100 microM dexamethasone increased HSP72 62% (P < 0.05). HSP27 and HSP60 were unchanged. The selective increase in HSP72 was associated with protection of the cardiac myocytes from hypoxia and reoxygenation. We conclude that dexamethasone is a novel inducer of the heat shock response.
Sun
L
L
Cardiology Research, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
Chang
J
J
Kirchhoff
S R
SR
Knowlton
A A
AA
D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000032:analysis / Q000096:biosynthesis; D004396:Coloring Agents / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics
D018834:Chaperonin 60; D004396:Coloring Agents; D005938:Glucocorticoids; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue