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 effect against ischemia/reperfusion injury. Here, we studied whether other hsps are also involved in cardioprotection. Using rat heart-derived H9c2 myocytes, we observed that preheating at 43 degreesC for 20 min conferred resistance to hydrogen peroxide (H2O2). The resistance to mild H2O2 toxicity (3-5 micro mol/10(7) cells) appeared early and persisted, whereas the resistance to moderate H2O2 toxicity (6-9 micro mol/10(7) cells) was detectable only at 20-44 h post heat shock. No resistance was observed at higher doses of hydrogen peroxide (10-12 micro mol/10(7) cells), indicating that severe toxicity exceeds the capacity of the induced 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). Nuclear translocations of hsp70i and hsp70c also occurred upon heat stimulation. A homogeneous distribution of the accumulated hsp70i and hsp70c throughout the nuclei and cytoplasm paralleled the development of heat-induced resistance to moderate H2O2 challenge. Application of another hsp inducer, ethyl alcohol, evoked a similar pattern of H2O2 resistance, and hsp induction and distribution. Our results suggest that induction and subcellular distribution of hsp70s contribute importantly to cellular antioxidant defenses, and that a co-operation between hsp70i and hsp70c may improve cardiac preservation during oxidative insult.
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Southern Illinois University School of Medicine, Department of Medicine/Pharmacology, Springfield, IL 62794, USA.
Chong
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Owen
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Dillmann
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Chang
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Lai
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D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000633:toxicity; D019157:Ischemic Preconditioning, Myocardial; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D000431:Ethanol; D006861:Hydrogen Peroxide