Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion.
We tested the hypothesis that heat-shock protected myocardial Ca2+-cycling by sarcoplasmic reticulum from ischemia and reperfusion (I/R) injury. Twenty-four hours after increasing body temperature to 42 degrees C for 15 min, rat hearts were isolated, Langendorff-perfused, and subjected to 30 min ischemia then 30 min reperfusion. Left ventricles were homogenized and their ionized Ca2+ concentration monitored with indo- during Ca2+-uptake in the presence and absence of the Ca2+-release channel (CRC) modulator ryanodine. Tissue content of heat-shock protein 72 (HSP 72) was analyzed. Exposure to I/R resulted in a 37% enhancement of CRC activity but no effect on Ca2+-pumping activity, resulting in 25% decreased net Ca2+-uptake activity. Pre-exposure to heat-shock resulted in a 10-fold increase in HSP 72, and a 25% enhancement of maximal Ca2+-pumping activity which counteracted the effect of I/R on CRC and net Ca2+-uptake activities. This protection of SR Ca2+-cycling was associated with partial protection of myocardial physiological performance. Net Ca2+-uptake activity was correlated with the left ventricular developed pressure and its rate of change. We conclude that one of the mechanisms by which heat-shock protects myocardium from I/R injury is to upregulate SR Ca2+-pumping activity to counteract the enhanced SR Ca2+-release produced by I/R.
O'Brien
P J
PJ
The Procter & Gamble Company, Human Safety Department, Cincinnati, Ohio 45253-8707, USA.
Li
G O
GO
Locke
M
M
Klabunde
R E
RE
Ianuzzo
C D
CD
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation
D015220:Calcium Channels; D006360:Heat-Shock Proteins; D000252:Calcium-Transporting ATPases; D002118:Calcium