Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling

Amanda Zatta, Hajime Kin, George Lee, Ningping Wang, Rong Jiang, Robert Lust, James Reeves, James Mykytenko, Robert Guyton, Zhi-Qing Zhao, Jakob Vinten-Johansen

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Abstract

Abstract Objective: Using non-selective and selective protein kinase C (PKC) ( and y isoform inhibitors, we tested the hypothesis that the cardioprotective phenotype invoked by postconditioning (postcon) is dependent on PKC signalling. Furthermore, we determined whether postconditioning alters pPKC( and/or pPKCy in cytosolic and mitochondrial fractions. Methods: Male Spraguea??Dawley rats underwent 30 min left coronary artery (LCA) occlusion followed by 3 h of reperfusion. Rats were randomised to the following groups: Untreated, no intervention either before or after LCA occlusion; Postcon, 3 cycles of 10-s full reperfusion and 10-s re-occlusion, initiated immediately at the onset of reperfusion; Chelerythrine (non-selective PKC inhibitor, 5 mg/kg) T postcon; Rottlerin (PKCy inhibitor, 0.3 mg/kg) T postcon; KIE1-1 (PKC( inhibitor, 3.8 mg/kg) T postcon. A subset of rats was employed to assess pPKC( and/or pPKCy in sham, Isch/RP (30-min LCA occlusion followed by 30-min reperfusion), and postcon-treated hearts. Results: Infarct size, expressed as area of necrosis as a percentage of the area at risk, AN/AAR ( ), was significantly reduced by postcon compared to control (untreated) rats (39T2 vs. 53T1 in control, P 2-fold decrease) compared to Isch/RP. Conclusion: These data suggest that postcon modulates PKC during early reperfusion by increasing PKC( expression and translocation to a site other than the outer mitochondrial membrane, and limits translocation of PKCy to mitochondria and associated deleterious signalling.
Original languageEnglish
Pages (from-to)315 - 324
Number of pages10
JournalCardiovascular Research
Volume70
Issue number2
Publication statusPublished - 2006

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