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 stre sses. Overexpression of HSP72 is cardioprotective. We were interested in th e regulation of heat-shock factor (HSF), the transcription factor for HSP g enes. Previously we have observed that the inflammatory cytokine tumor necr osis factor-alpha increases HSP78 levels and postulated that dexamethasone might effect the heat shock response. In the adult rat cardiac myocyte we f ound that treatment with either low (10 mu M)- or high (100 mu M)-dose dexa methasone activated HSF by 2-6 h as determined by gel shift assay without e vidence of cytotoxicity. Although HSF activation is a key step in expressio n of HSP72, this may not result in an increase in HSP72. We found that 10 m u M dexamethasone increased HSP72 38%, and 100 mu M dexamethasone increased HSP72 62% (P < 0.05). HSP27 and HSP60 were unchanged. The selective increa se in HSP72 was associated with protection of the cardiac myocytes from hyp oxia and reoxygenation. We conclude that dexamethasone is a novel inducer o f the heat shock response.