【摘 要】
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Background: Our previous finding showed that brain ischemic preconditioning mediates neuroprotection through endoplasmic reticulum (ER) stress-induced autop
【机 构】
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Department of Pharmacology and Laboratory of Aging and Nervous Diseases
【出 处】
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The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Background: Our previous finding showed that brain ischemic preconditioning mediates neuroprotection through endoplasmic reticulum (ER) stress-induced autophagy.This study was aimed to explore the role of ER chaperone GRP78 in IPC induced autophagy activation in neural cells.Results: Ischemic preconditioning (IPC) and oxygen glucose deprivation (OGD) models were established in rat pheochromocytoma (PC12) cells and primary cultured murine cortical neurons.IPC exerted neuroprotection against subsequent OGD injury in both PC12 cells and primary cortical neurons.IPC increased GRP78 expression and activated autophagy, as evidenced by upregulated LC3 and Beclin1, and increased formation of autophagosomes.BAPTA(dibromo-1,2-bis(aminophenoxy)ethane N,N,N9,N9-tetra acetic acid, 0.125-2 μM) and small interfering RNA targeted GRP78 abrogated IPC induced neuroprotection, and decreased the expression of GRP78, LC3Ⅱ/LC3Ⅰ and Beclin1.By contrast, GRP78 overexpression by lentiviral vector mediated GRP78 overexpression (LV-GRP78) strengthened resistance of PC12 cells to OGD injury, and increased LC3 and Beclin1 expression.Moreover, knockdown of GRP78 in stably GRP78 overexpressing PC12 cells abolished the upregulation of LC3Ⅱ/LC3Ⅰ.GRP78 might activate autophagy through AMPK-mTOR pathway.Conclusion: These results suggest that IPC-induced GRP78 upregulation might be involved in autophagy activation, and hence exerts protection against ischemic injury in neural cells.
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