CONSTITUTIVE AND INDUCIBLE HSP70S ARE INVOLVED IN OXIDATIVE RESISTANCE EVOKED BY HEAT-SHOCK OR ETHANOL

Improved cardiac post-ischemic recovery after whole-body hyperthermia is correlated with an increased expression of the heat shock proteins (hsps). The inducible hsp70 (hsp70i) has a known cardioprotective effe ct against ischemia/reperfusion injury. Here, we studied whether other hsps are also involved in cardioprotection. Using rat heart-derived H 9c2 myocytes, we observed that preheating at 43 degrees C for 20 min c onferred resistance to hydrogen peroxide (H2O2). The resistance to mil d H2O2 toxicity (3-5 mu mol/10(7) cells) appeared early and persisted, whereas the resistance to moderate H2O2 toxicity (6-9 mu mol/10(7) ce lls) was detectable only at 20-44 h post heat shock. No resistance was observed at higher doses of hydrogen peroxide (10-12 mu mol/10(7) cel ls), indicating that severe toxicity exceeds the capacity of the induc ed protective mechanism. Coincidentally, this thermal regimen elicited a rapid and prolonged increase in the cellular level of hsp70i, and a delayed and transient induction of the constitutive hsp70 (hsp70c). N uclear translocations of hsp70i and hsp70c also occurred upon heat sti mulation. A homogeneous distribution of the accumulated hsp70i and hsp 70c throughout the nuclei and cytoplasm paralleled the development of heat-induced resistance to moderate H2O2 challenge. Application of ano ther hsp inducer, ethyl alcohol, evoked a similar pattern of H2O2 resi stance, and hsp induction and distribution. Our results suggest that i nduction and subcellular distribution of hsp70s contribute importantly to cellular antioxidant defenses, and that a co-operation between hsp 70i and hsp70c may improve cardiac preservation during oxidative insul t. (C) 1998 Academic Press Limited.