Regulation of prostaglandin A1-induced heat shock protein expression in isolated cardiomyocytes.
Prostaglandins of the A-type (PGAs) induce heat shock protein (HSP) synthesis in a wide variety of mammalian cells resulting in protection against cellular stresses. The effect of PGAs on HSP-induction in cardiac myocytes is unknown. Therefore, we investigated the effect of PGA1 on HSP synthesis in adult rat cardiac myocytes. After 24 h of treatment, HSP72 was significantly increased 2.9-, 5.6- and 5.0-fold by PGA1 used at concentrations of 10, 20 or 40 microg/ml, respectively (P<0.05). However, the PGA1-concentration of 40 microg/ml, was found to be cytotoxic as evidenced by the release of LDH. In addition to HSP72, HSP32 was significantly increased by PGA1. The HSP32 induction was more vigorous with a marked increase with only 4 microg/ml of PGA1. No differences in the levels of HSP27, HSP60 or HSP90 were detected. When isolated cardiac myocytes were treated with PGA1, clear activation of heat shock factor (HSF) 1, one of the transcription factors for HSPs, was observed. In addition, another stress-induced transcription factor NFkappaB was also activated by PGA exposure. Despite the significant upregulation of both HSP72 and HSP32 cytoprotective properties against hypoxia and reoxygenation were absent. In conclusion, these experiments show for the first time that PGA1 induces differential expression of heat shock proteins in cardiac myocytes probably mediated through the activation of both HSF1 and NFkappaB.
Cornelussen
R N
RN
Baylor College of Medicine and the VA Medical Center, Houston, TX, USA.
Gupta
S
S
Knowlton
A A
AA
D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis*; D011454:Prostaglandins A / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D016328:NF-kappa B; D011454:Prostaglandins A; D014157:Transcription Factors; D007770:L-Lactate Dehydrogenase; C100573:prostaglandin A1