Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro |
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Authors: | Bhuiyan Mohammad Iqbal Hossain Jung Seo Yun Kim Hyoung Ja Lee Yong Sup Jin Changbae |
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Institution: | (1) Department of Anesthesiology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China;(2) Department of Pathophysiology, Institute of Integrated Traditional Chinese and Western Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China;(3) School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;(4) Department of Cardiology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China; |
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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. |
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