OXIDANT STRESS INCREASES HEAT-SHOCK PROTEIN-70 MESSENGER-RNA IN ISOLATED-PERFUSED RAT-HEART

Ischemia/reperfusion (I/R) and preconditioning of the heart by coronar y artery occlusions increase expression of heat shock protein 70 (HSP 70). Because free radicals are generated during I/R, we hypothesized t hat the oxidant stress might contribute to an increased expression of HSP 70. Isolated rat hearts were perfused with free radical-generating systems such as xanthine/ xanthine oxidase (X/XO), irradiated rose be ngal (RB) generating singlet oxygen, and H2O2 for 15 min followed by 3 0 min of recovery period. Significant decrease in developed pressure a nd coronary flow occurred after perfusion with X/XO, H2O2, and RB. Dur ing I/R, the developed pressure and coronary flow were 60 +/- 8 and 80 +/- 5%, respectively, of control, which improved significantly with s uperoxide dismutase. The expression of HSP 70 mRNA increased over 13-f old in hearts perfused with X/XO, 6- to 7-fold with RB, and over 5-fol d with H2O2. With I/R, an over 10-fold increase in HSP 70 mRNA was obs erved, which decreased significantly in the presence of superoxide dis mutase. These results demonstrate that oxidant stress directly increas es HSP 70 mRNA in the rat heart. It is concluded that one of the poten tial mechanisms of expression of HSP 70 by I/R may be oxygen radicals.