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

J Cereb Blood Flow Metab. 2001 Apr;21(4):351-60. doi: 10.1097/00004647-200104000-00004.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain Ischemia / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Gerbillinae
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Ischemic Preconditioning*
  • Male
  • Neurons / cytology
  • Neurons / enzymology*
  • Phosphorylation
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Serine / metabolism
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • Serine
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Wortmannin