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 PGA1on 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 PGA1used at concentrations of 10, 20 or 40μ g/ml, respectively (P<0.05). However, the PGA1-concentration of 40 μ g/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 μ g/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 NFκB 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 PGA1induces differential expression of heat shock proteins in cardiac myocytes probably mediated through the activation of both HSF1and NFκB.