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Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion

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Abstract

We tested the hypothesis that heat-shock protected myocardialCa2+-cycling by sarcoplasmic reticulum from ischemia and reperfusion (I/R)injury. Twenty-four hours after increasing body temperature to 42°C for15 min, rat hearts were isolated, Langendorff-perfused, and subjected to 30min ischemia then 30 min reperfusion. Left ventricles were homogenized andtheir ionized Ca2+ concentration monitored with indo-1 during Ca2+-uptake inthe presence and absence of the Ca2+-release channel (CRC) modulatorryanodine. Tissue content of heat-shock protein 72 (HSP 72) was analyzed.Exposure to I/R resulted in a 37% enhancement of CRC activity but noeffect on Ca2+-pumping activity, resulting in 25% decreased netCa2+-uptake activity. Pre-exposure to heat-shock resulted in a 10-foldincrease in HSP 72, and a 25% enhancement of maximal Ca2+-pumpingactivity which counteracted the effect of I/R on CRC and net Ca2+-uptakeactivities. This protection of SR Ca2+-cycling was associated with partialprotection of myocardial physiological performance. Net Ca2+-uptake activitywas correlated with the left ventricular developed pressure and its rate ofchange. We conclude that one of the mechanisms by which heat-shock protectsmyocardium from I/R injury is to upregulate SR Ca2+-pumping activity tocounteract the enhanced SR Ca2+-release produced by I/R.

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Authors and Affiliations

  1. Human Safety Department, The Procter & Gamble Company, 500 Miami Valley Laboratories, P.O. Box 538707, Cincinnati, Ohio, 45253-8707, USA

    Pj O'Brien

  2. Department of Pharmacology and Toxicology, School of Medicine, 501 North Columbia Rd, Grand Forks, North Dakota, 58202, USA

    Go Li

  3. Deborah Research Institute, Browns Mills, NJ, 08015-1799, USA

    M Locke, Re Klabunde & Cd Ianuzo

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O'Brien, P., Li, G., Locke, M. et al. Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion. Mol Cell Biochem 173, 135–143 (1997). https://doi.org/10.1023/A:1006840013439

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