Major Role of the PI3K/Akt Pathway in Ischemic Tolerance Induced by Sublethal Oxygen-Glucose Deprivation in Cortical Neurons In Vitro
- Major Role of the PI3K/Akt Pathway in Ischemic Tolerance Induced by Sublethal Oxygen-Glucose Deprivation in Cortical Neurons In Vitro
- 뷰티안; 정서윤; 김형자; 이용섭; 진창배
- Ischemic tolerance; Preconditioning; PI3K/Akt; MAPK; Oxygen-glucose deprivation; Cortical neuron
- Issue Date
- Archives of pharmacal research
- VOL 34, NO 6, 1023-1034
- 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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