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PROTEIN-KINASE-C - ITS ROLE IN ISCHEMIC PRECONDITIONING IN THE RAT

SPEECHLYDICK, ME; MOCANU, MM; YELLON, DM; (1994) PROTEIN-KINASE-C - ITS ROLE IN ISCHEMIC PRECONDITIONING IN THE RAT. CIRC RES , 75 (3) 586 - 590.

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Abstract

The present study investigated whether protein kinase C (PE;C) 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. VR 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). Inhibition of PE;C with chelerythrine abolished protection, there being no significant difference in I/R between control and the chelerythrine-treated preconditioned group (group C, 58.6 +/- 5.0%; group PCC, 62.3 +/- 5.78). Chelerythrine and the vehicle DMSO had no direct influence on infarct size (group CC, 63.2 +/- 2.2%; group DMSO, 60.7 +/- 9.9%). Thus, PKC stimulation with the diacylglycerol analogue DOG resulted in protection, and PKC inhibition with chelerythrine abolished protection. The finding that treatment with a PKC stimulator gives a similar degree of protection against infarction as that seen after ischemic preconditioning and that this protection can be blocked by a PKC inhibitor provides support for the hypothesis that PKC plays an important role in ischemic preconditioning.

Type:Article
Title:PROTEIN-KINASE-C - ITS ROLE IN ISCHEMIC PRECONDITIONING IN THE RAT
Keywords:ISCHEMIC PRECONDITIONING, PROTEIN KINASE C, MYOCARDIAL PROTECTION, INFARCTION, INFARCT SIZE, ACTIVATION, HEART, MYOCARDIUM, ADENOSINE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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