Protein kinase C. Its role in ischemic preconditioning in the rat.
The present study investigated whether protein kinase C (PKC) plays a role in ischemic preconditioning in the rat heart. Chelerythrine, a specific antagonist of PKC, and 1,2-dioctanoyl-sn-glycerol (DOG), a diacylglycerol analogue and specific antagonist of PKC, were used to determine whether preconditioning could be blocked or triggered, respectively. Sprague-Dawley rats were anesthetized and instrumented for coronary occlusion and reperfusion. All animals were subjected to 45 minutes of regional ischemia (ISC) followed by 2.5 hours of reperfusion. The preconditioning protocol consisted of 5 minutes of ischemia and then 10 minutes of reperfusion. There were six groups: (1) control (group C, n = 5), (2) preconditioned and ISC (group PC, n = 6), (3) chelerythrine given 2 minutes before ISC (group CC, n = 5), (4) preconditioned and chelerythrine given 2 minutes before ISC (group PCC, n = 6), (5) DOG (dissolved in dimethylsulfoxide [DMSO]) given 10 minutes before ISC (group CD, n = 5), and (6) DMSO given 10 minutes before ISC (group DMSO, n = 3). The end point was infarct size measured using triphenyl tetrazolium chloride and expressed as a percentage of the volume at risk (I/R), measured with fluorescent particles. I/R was significantly reduced by preconditioning (group C, 58.6 +/- 5.0%; group PC, 32.7 +/- 6.3%; P < .01) and by the PKC agonist DOG, which reduced I/R to a similar extent as preconditioning (group C, 58.6 +/- 5.0%; group CD, 28.0 +/- 7.0%; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Speechly-Dick
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ME
Hatter Institute for Cardiovascular Studies, University College London Hospitals, England.
Mocanu
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MM
Yellon
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D000470:Alkaloids; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D053119:Benzophenanthridines; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009929:Organ Size / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D053119:Benzophenanthridines; D004075:Diglycerides; D010617:Phenanthridines; C044295:1,2-dioctanoylglycerol; C016299:chelerythrine; D011493:Protein Kinase C