Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway.

Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway.
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姜黄素对缺血性脑损伤的神经保护作用涉及 Akt/Nrf2 通路

DOI:
10.1371/journal.pone.0059843
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhao Y
Zhao Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wu J;Li Q;Wang X;Yu S;Li L;Wu X;Chen Y;Zhao J;Zhao Y

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氧化损伤在许多中枢神经系统疾病中起着关键作用。本研究旨在探讨姜黄素对实验性卒中抗氧化作用的分子机制。用缺氧缺糖/复氧(OGD/R)法模拟原代培养的大脑皮层神经元的缺血性损伤。姜黄素可拮抗OGD诱导的细胞内NAD(P)H:QO1表达的快速增加,与减轻细胞损伤的作用平行。姜黄素可恢复OGD引起的Akt磷酸化水平的降低。因此,NQO1的表达和核因子-红系相关因子2(NRF2)与抗氧化反应元件(ARE)的结合活性增加。LY294002可阻断姜黄素诱导的磷酸化Akt的增加,并取消相关的保护作用。成年雄性SD大鼠大脑中动脉短暂性闭塞60min。姜黄素可显著缩小脑梗塞面积。姜黄素还显著降低大脑中动脉闭塞(MCAO)大鼠的氧化应激水平;因此,这些作用均被LY294002抑制。综上所述,这些发现为姜黄素保护神经元免受缺血损伤提供了证据,这种神经保护作用涉及Akt/Nrf2通路。此外,Nrf2参与了姜黄素对氧化损伤的神经保护作用。
Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE) were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage.
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