Mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC ɛ) peptide activator or inhibitor in rat ischemia/reperfusion injury.

Autor: Teng, Jane, Kay, Helen, Chen, Qian, Adams, Jovan, Grilli, Christopher, Guglielmello, Giuseppe, Zambrano, Christopher, Krass, Samuel, Bell, Adrian, Young, Lindon
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology; Jul2008, Vol. 378 Issue 1, p1-15, 15p, 2 Diagrams, 3 Charts, 5 Graphs
Abstrakt: The role of protein kinase C epsilon (PKC ɛ) in polymorphonuclear leukocyte (PMN)-induced myocardial ischemia/reperfusion (MI/R) injury and novel-related mechanisms, such as regulation of vascular endothelium nitric oxide (NO) and hydrogen peroxide (H2O2) release from blood vessels, have not been previously evaluated. A cell-permeable PKC ɛ peptide activator (1–10 μM) significantly increased endothelial NO release from non-ischemic rat aortic segments ( p < 0.01). By contrast, PKC ɛ peptide inhibitor (1–10 μM) dose-dependently decreased NO release ( p < 0.01). Then, these corresponding doses of PKC ɛ activator or inhibitor were examined in MI/R. The PKC ɛ inhibitor (5 μM given during reperfusion, n = 6) significantly attenuated PMN-induced postreperfused cardiac contractile dysfunction and PMN adherence/infiltration (both p < 0.01), and expression of intracellular adhesion molecule-1 (ICAM-1; p < 0.05). By contrast, only PKC ɛ activator pretreated hearts (5 μM PKC ɛ activator given before ischemia (PT), n = 6), not PKC ɛ activator given during reperfusion (5 μM, n = 6) exerted significant cardioprotection ( p < 0.01). Moreover, the NO synthase inhibitor, NG-nitro- l-arginine methyl ester, did not block the cardioprotection of PKC ɛ inhibitor, whereas it completely abolished the cardioprotective effects of PKC ɛ activator PT. In addition, PKC ɛ inhibitor (0.4 mg/kg) significantly decreased H2O2 release during reperfusion in a femoral I/R model ( p < 0.01). Therefore, the cardioprotection of PKC ɛ inhibitor maybe related to attenuating ICAM-1 expression and H2O2 release during reperfusion. By contrast, the cardioprotective effects of PKC ɛ activator PT may be mediated by enhancing vascular endothelial NO release before ischemia. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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