Post-ischemic activation of protein kinase C ε protects the hippocampus from cerebral ischemic injury via alterations in cerebral blood flow.
Protein kinase C (PKC) is a family of serine/threonine-isozymes that are involved in many signaling events in normal and disease states. Previous studies from our lab have demonstrated that ɛPKC plays a pivotal role in neuroprotection induced by ischemic preconditioning. However, the role of ɛPKC during and after brain ischemia is not clearly defined. Therefore, in the present study, we tested the hypothesis that activation of ɛPKC during an ischemic event is neuroprotective. Furthermore, other studies have demonstrated that ɛPKC mediates cerebral ischemic tolerance in the rat brain by decreasing vascular tone. Thus, we also tested the effects of ɛPKC activation during ischemia on cerebral blood flow (CBF). We found that ψɛ-Receptors for Activated C Kinase (RACK), a ɛPKC-selective peptide activator, injected intravenously 30min before induction of global cerebral ischemia conferred neuroprotection in the CA1 region of the rat hippocampus. Moreover, measurements of CBF before, during, and after cerebral ischemia revealed a significant reduction in the reperfusion phase of rats pretreated with ψɛRACK as compared to Tat peptide (vehicle). Our results suggest that ɛPKC can protect the rat brain against ischemic damage by regulating CBF. Thus, ɛPKC may be one of the treatment modalities against ischemic injury.
Department of Neurology, University of Miami, Miami, FL 33101, USA.
D
D
Della-Morte
A P
AP
Raval
K R
KR
Dave
H W
HW
Lin
M A
MA
Perez-Pinzon
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000008:administration & dosage; D013997:Time Factors
D018696:Neuroprotective Agents; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D051744:Protein Kinase C-epsilon