title: Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro.
abstract: Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD imposed 12 h before lethal 3-h OGD. The time-course studies of relative phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of their involvement in ischemic tolerance. However, there were significant increases in Akt phosphorylation levels during the reperfusion period following preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and GSK-3β were also found to be inactivated during that reperfusion period. Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.
authors: Integrated Omics Center, Life/Health Division, Korea Institute of Science and Technology (KIST), P.O. Box 131, Cheongryang, Seoul 130-650, Korea.
authors: Mohammad Iqbal Hossain
authors: MI
authors: Bhuiyan
authors: Seo Yun
authors: SY
authors: Jung
authors: Hyoung Ja
authors: HJ
authors: Kim
authors: Yong Sup
authors: YS
authors: Lee
authors: Changbae
authors: C
authors: Jin
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D019194:Ischemic Preconditioning / Q000379:methods*; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D005947:Glucose; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin