Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus.
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.
Yano
S
S
Department of Neurosurgery, Kumamoto University School of Medicine, Honjo Kumamoto, Japan.
Morioka
M
M
Fukunaga
K
K
Kawano
T
T
Hara
T
T
Kai
Y
Y
Hamada
J
J
Miyamoto
E
E
Ushio
Y
Y
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin