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Mechanisms Related to the Cardioprotective Effects of Protein Kinase C Epsilon (PKC Epsilon) Peptide Activator or Inhibitor in Rat Ischemia/Reperfusion Injury
Naunyn-Schmiedebergs Archives of Pharmacology
  • Jane Chun-wen Teng, Philadelphia College of Osteopathic Medicine
  • Helen Kay, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Jovan S Adams, Philadelphia College of Osteopathic Medicine
  • Christopher Grilli, Philadelphia College of Osteopathic Medicine
  • Giuseppe Guglielmello, Philadelphia College of Osteopathic Medicine
  • Christopher Zambrano, Philadelphia College of Osteopathic Medicine
  • Samuel Krass, Philadelphia College of Osteopathic Medicine
  • Adrian Bell, Philadelphia College of Osteopathic Medicine
  • Lindon H. Young, Philadelphia College of Osteopathic Medicine
Document Type
Article
Publication Date
7-1-2008
Abstract
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 (p < 0.01). By contrast, PKC epsilon peptide inhibitor (1-10 microM) dose-dependently decreased NO release (p < 0.01). 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 p < 0.01), and expression of intracellular adhesion molecule-1 (ICAM-1; p < 0.05). 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 (p < 0.01). 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 (p < 0.01). 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.
PubMed ID
18496674
Comments

This article was published in Naunyn-Schmiedebergs Archives of Pharmacology, Volume 378, Issue 1, July 2008, Pages 1-15.

The published version is available at http://dx.doi.org/10.1007/s00210-008-0288-5

Copyright © 2008 by Springer, Part of Springer Science+Business Media

Citation Information
Jane Chun-wen Teng, Helen Kay, Qian Chen, Jovan S Adams, et al.. "Mechanisms Related to the Cardioprotective Effects of Protein Kinase C Epsilon (PKC Epsilon) Peptide Activator or Inhibitor in Rat Ischemia/Reperfusion Injury" Naunyn-Schmiedebergs Archives of Pharmacology Vol. 378 Iss. 1 (2008) p. 1 - 15
Available at: http://works.bepress.com/qian_chen/9/