title: epsilonPKC confers acute tolerance to cerebral ischemic reperfusion injury.
abstract: 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.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bright
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Sun
authors.forename: Midori A
authors.initials: MA
authors.lastname: Yenari
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000818:Animals; D002545:Brain Ischemia; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D010455:Peptides / Q000008:administration & dosage; D051744:Protein Kinase C-epsilon / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D051744:Protein Kinase C-epsilon