Protein kinase C-delta mediates adenosine A3 receptor-induced delayed cardioprotection in mouse.
We investigated the role of protein kinase C in adenosine A3 receptor (A3AR)-induced delayed cardioprotection in the mouse heart. Mice were treated with selective A3AR agonist N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA). Twenty-four hours later, hearts were perfused in the Langendorff mode and subjected to 30 min of global ischemia and 30 min of reperfusion. Infarct size was determined by computer morphometry of tetrazolium-stained sections, and ventricular function was monitored by inserting a fluid-filled balloon into the left ventricle (LV). Chelerythrine chloride (CHE, 5.0 mg/kg) and rottlerin (Rot, 0.3 mg/kg) were given 30 min before IB-MECA to block total and PKC-delta isoforms, respectively. IB-MECA caused postischemic reduction in necrosis and improvement in ventricular function, which was abolished by CHE. Western blot analysis demonstrated translocation of the PKC-delta isoform but not the alpha, epsilon, xi, eta isoform(s) from cytoplasm to the membrane fraction after 30 min of IB-MECA administration. A3AR antagonist MRS-1191 and CHE blocked the translocation of PKC-delta. Furthermore, IB-MECA-induced increase in nuclear factor-kappaB binding was diminished by CHE. These results provide direct evidence of an essential role of PKC, and more specifically, PKC-delta in A3AR-induced delayed cardioprotection.
Zhao
Ting Cun
TC
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Kukreja
Rakesh C
RC
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D015153:Blotting, Western; D002467:Cell Nucleus / Q000201:enzymology / Q000502:physiology; D003600:Cytosol / Q000201:enzymology / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006331:Heart Diseases / Q000517:prevention & control*; D006334:Heart Function Tests; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C107728:MRS 1191; D016328:NF-kappa B; D010617:Phenanthridines; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; C016299:chelerythrine; D011493:Protein Kinase C; D000241:Adenosine