Mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC ɛ) peptide activator or inhibitor in rat ischemia/reperfusion injury
| Autor: | Jane Chun-wen Teng, Jovan Adams, Qian Chen, Helen Kay, Giuseppe Guglielmello, Christopher Grilli, Christopher Zambrano, Lindon H. Young, Adrian Bell, Samuel Krass |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cardiotonic Agents Endothelium Ischemia Protein Kinase C-epsilon Pharmacology Nitric Oxide Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound medicine Animals Endothelial dysfunction Aorta Protein kinase C Cardioprotection Dose-Response Relationship Drug Activator (genetics) Hydrogen Peroxide General Medicine Intercellular Adhesion Molecule-1 medicine.disease Rats medicine.anatomical_structure Gene Expression Regulation chemistry Biochemistry Reperfusion Injury Endothelium Vascular Oligopeptides Reperfusion injury |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 378:1-15 |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-008-0288-5 |
| Popis: | The role of protein kinase C epsilon (PKC epsilon) 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 epsilon peptide activator (1-10 microM) significantly increased endothelial NO release from non-ischemic rat aortic segments (p0.01). By contrast, PKC epsilon peptide inhibitor (1-10 microM) dose-dependently decreased NO release (p0.01). Then, these corresponding doses of PKC epsilon activator or inhibitor were examined in MI/R. The PKC epsilon inhibitor (5 microM given during reperfusion, n=6) significantly attenuated PMN-induced postreperfused cardiac contractile dysfunction and PMN adherence/infiltration (both p0.01), and expression of intracellular adhesion molecule-1 (ICAM-1; p0.05). By contrast, only PKC epsilon activator pretreated hearts (5 muM PKC epsilon activator given before ischemia (PT), n = 6), not PKC epsilon activator given during reperfusion (5 microM, n=6) exerted significant cardioprotection (p0.01). Moreover, the NO synthase inhibitor, N(G)-nitro-L: -arginine methyl ester, did not block the cardioprotection of PKC epsilon inhibitor, whereas it completely abolished the cardioprotective effects of PKC epsilon activator PT. In addition, PKC epsilon inhibitor (0.4 mg/kg) significantly decreased H(2)O(2) release during reperfusion in a femoral I/R model (p0.01). Therefore, the cardioprotection of PKC epsilon inhibitor maybe related to attenuating ICAM-1 expression and H2O2 release during reperfusion. By contrast, the cardioprotective effects of PKC epsilon activator PT may be mediated by enhancing vascular endothelial NO release before ischemia. |
| Databáze: | OpenAIRE |
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