Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus

Shigetoshi Yano, Motohiro Morioka, Kohji Fukunaga, Takayuki Kawano, Tsuyoshi Hara, Yutaka Kai, Jun Ichiro Hamada, Eishichi Miyamoto, Yukitaka Ushio

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number4
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Keywords

  • Akt
  • Apoptosis
  • Cerebral ischemia
  • Gerbil brain
  • Tolerance
  • Wortmannin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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