Reactive Oxygen Species Play an Important Role in the Activation of Heat Shock Factor 1 in Ischemic-Reperfused Heart

Background—The myocardial protective role of heat shockprotein (HSP) has been demonstrated. Recently, we reported that ischemia/reperfusion induced a significant activation of heat shock factor(HSF) 1 and an accumulation of mRNA for HSP70and HSP90. We examined the role of reactive oxygen species (ROSs) in the induction of stress response in the ischemic-reperfused heart. Methods and Results—Rat hearts were isolated and perfused with Krebs-Henseleit bufferby the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shockelement. Induction of mRNA for HSP70and HSP90was examined by Northern blot analysis. Repetitive ischemia/reperfusion, which causes recurrent bursts of free radical generation, resulted in burst activation of HSF1, and this burst activation was significantly reduced with either allopurinol1 mmol/L (an inhibitor of xanthine oxidase) or catalase 2×105 U/L (a scavenger of H2O2). Significant activation of HSF1was ob...