The neuroprotective effects of curcumin are associated with the regulation of the reciprocal function between autophagy and HIF-1α in cerebral ischemia-reperfusion injury
The neuroprotective effects of curcumin are associated with the regulation of the reciprocal function between autophagy and HIF-1α in cerebral ischemia-reperfusion injury
复制标题
姜黄素的神经保护作用与脑缺血再灌注损伤中自噬和HIF-1α相互作用的调节有关
DOI：
10.2147/dddt.s194182
复制
发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Feng, Juan
中科院分区：
文献类型：
--
作者：
Hou, Yang;Wang, Jue;Feng, Juan
目的：姜黄素对缺血再灌注损伤的有益的神经保护作用已经被证明。本研究探讨姜黄素是否通过抑制自噬和缺氧诱导因子-1 α（hypoxia inducible factor-1 alpha，HIF-1 alpha）发挥神经保护作用。材料与方法：建立PC 12细胞缺氧缺糖再灌注（OGD/R）模型，模拟脑缺血再灌注损伤。使用CellTiter 96（R）AQ（ueous）评价细胞活力。单溶液细胞增殖测定。使用流式细胞术评估细胞凋亡。用Western blot检测HIF-1 α和自噬相关蛋白LC 3和P62的表达水平。使用荧光显微镜基于自噬区室的数目定量估计自噬通量。此外，将3-甲基腺嘌呤（3-MA）给予PC 12细胞以研究自噬如何影响HIF-1 α。结果：姜黄素可降低OGD/R条件下细胞的死亡和凋亡，抑制自噬和HIF-1 α的表达，与3-MA处理或HIF-1 α下调一致。结论：姜黄素对缺血再灌注损伤具有神经保护作用，其机制可能与调节自噬和HIF-1 α之间的相互作用有关。
Purpose: The beneficial, neuroprotective effects of curcumin against ischemia-reperfusion injury have been demonstrated. In the present study, whether curcumin exerts neuroprotective effects associated with the inhibition of autophagy and hypoxia inducible factor-1 alpha (HIF-1 alpha) was investigated.Materials and methods: PC12 cellular model of oxygen glucose deprivation/reperfusion (OGD/R) has been developed to mimic cerebral ischemia-reperfusion injury. Cell viability was evaluated using the CellTiter 96 (R) AQ(ueous). One Solution Cell Proliferation Assay. Apoptosis was assessed using flow cytometry. The expression levels of HIF- la and autophagy-associated proteins, LC3 and P62, were examined using Western blot. The autophagy flux was quantitatively estimated based on the number of autophagic compartments using fluorescence microscopy. In addition, 3-methyladenine (3-MA) was administered to PC12 cells to investigate how autophagy affects HIF-1 alpha. Moreover, the inhibitory effects of HIF-1 alpha on autophagy activation level were examined.Results: In this study, curcumin decreased the death and apoptosis of cells, and inhibited autophagy and HIF-1 alpha under OGD/R conditions, consistent with 3-MA treatment or HIF-1 alpha downregulation. Moreover, inhibition of autophagy caused a decrease in HIF-1 alpha, and the attenuation of HIF-1 alpha induced autophagy suppression under OGD/R conditions.Conclusion: The results of this study showed that curcumin exerts neuroprotective effects against ischemia-reperfusion, which is associated with the regulation of the reciprocal function between autophagy and HIF-1 alpha.