Differential effects of delta and epsilon protein kinase C in modulation of postischemic cerebral blood flow

Hung Wen Lin, David Della-Morte, John W. Thompson, Victoria L. Gresia, Srinivasan V. Narayanan, R. Anthony Defazio, Ami P. Raval, Isabel Saul, Kunjan R. Dave, Kahlilia C. Morris, Min Liang Si, Miguel A. Perez-Pinzon

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

Cerebral ischemia causes cerebral blood flow (CBF) derangements resulting in neuronal damage by enhanced protein kinase C delta (δPKC) levels leading to hippocampal and cortical neuronal death after ischemia. Contrarily, activation of εPKC mediates ischemic tolerance by decreasing vascular tone providing neuroprotection. However, whether part of this protection is due to the role of differential isozymes of PKCs on CBF following cerebral ischemia remains poorly understood. Rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after two-vessel occlusion plus hypotension. In an asphyxial cardiac arrest (ACA) model, rats treated with δV1-1 (pre- and postischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 and cortical neuronal death 7 days after ACA. On the contrary, εPKC-selective peptide activator, conferred neuroprotection in the CA1 region of the rat hippocampus 30 min before induction of global cerebral ischemia and decreased regional CBF during the reperfusion phase. These opposing effects of δv. εPKC suggest a possible therapeutic potential by modulating CBF preventing neuronal damage after cerebral ischemia.

Original languageEnglish (US)
Title of host publicationOxygen Transport to Tissue XXXIII
Pages63-69
Number of pages7
DOIs
StatePublished - Feb 1 2012

Publication series

NameAdvances in Experimental Medicine and Biology
Volume737
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lin, H. W., Della-Morte, D., Thompson, J. W., Gresia, V. L., Narayanan, S. V., Defazio, R. A., Raval, A. P., Saul, I., Dave, K. R., Morris, K. C., Si, M. L., & Perez-Pinzon, M. A. (2012). Differential effects of delta and epsilon protein kinase C in modulation of postischemic cerebral blood flow. In Oxygen Transport to Tissue XXXIII (pp. 63-69). (Advances in Experimental Medicine and Biology; Vol. 737). https://doi.org/10.1007/978-1-4614-1566-4_10