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Neurosci Lett. 2008 Aug 15;441(1):120-4. doi: 10.1016/j.neulet.2008.05.080. Epub 2008 May 27.

epsilonPKC confers acute tolerance to cerebral ischemic reperfusion injury.

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Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.


In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that epsilonPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of psiepsilonRACK, an epsilonPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of epsilonPKC by psiepsilonRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient epsilonPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection.

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