Bhuiyan, Mohammad Iqbal Hossain Jung, Seo Yun Kim, Hyoung Ja Lee, Yong Sup Jin, Changbae 2024-01-20T17:01:30Z 2024-01-20T17:01:30Z 2021-09-05 2011-06 0253-6269 https://pubs.kist.re.kr/handle/201004/130297 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-3 beta 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-3 beta. 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. English PHARMACEUTICAL SOC KOREA GLYCOGEN-SYNTHASE KINASE-3-BETA CEREBRAL-ISCHEMIA REGULATED KINASE CELL-DEATH ACTIVATION PHOSPHORYLATION SURVIVAL AKT BRAIN EXPRESSION Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro Article 10.1007/s12272-011-0620-3 1 ARCHIVES OF PHARMACAL RESEARCH, v.34, no.6, pp.1023 - 1034 ARCHIVES OF PHARMACAL RESEARCH 34 6 1023 1034 scie scopus kci ART001559315 000292306000022 2-s2.0-79960229383 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article GLYCOGEN-SYNTHASE KINASE-3-BETA CEREBRAL-ISCHEMIA REGULATED KINASE CELL-DEATH ACTIVATION PHOSPHORYLATION SURVIVAL AKT BRAIN EXPRESSION Ischemic tolerance Preconditioning PI3K/Akt MAPK Oxygen-glucose deprivation Cortical neuron