Eriodictyol protects against H2O2-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway
Eriodictyol protects against H2O2-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway
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圣草酚通过激活 Nrf2/ARE 信号通路防止 H2O2 诱导的神经元样 PC12 细胞死亡
DOI：
10.1016/j.neuint.2012.05.013
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发表时间：
2012-07-01
影响因子：
4.2
通讯作者：
Zhang, Xiumei
中科院分区：
文献类型：
--
作者：
Lou, Haiyan;Jing, Xu;Zhang, Xiumei
圣草酚是一种从中药青兰中分离出来的黄酮类化合物，长期以来一直被认为是一种抗氧化剂。本研究旨在探讨圣草酚对培养的大鼠嗜铬细胞瘤细胞（PC12细胞）过氧化氢（H2O2）诱导的神经毒性的保护作用及其可能的机制。为此，培养分化的 PC12 细胞，并在不存在或存在圣草酚（20、40 和 80 μM）的情况下暴露于 200 μM H2O2。此外，还研究了 Nrf2/ARE 神经保护途径在圣草酚介导的针对 H2O2 诱导的神经毒性的保护中的潜在贡献。结果表明，通过 MIT 和细胞凋亡测定测量，在圣草酚存在的情况下，H2O2 诱导的细胞死亡可以被抑制。进一步的研究表明，圣草酚诱导Nrf2核转位，增强家庭加氧酶（HO-1）和γ-谷氨酰半胱氨酸合成酶（γ-GCS）的表达，并增加细胞内谷胱甘肽的水平。用 Nrf2 小干扰 RNA 处理 PC12 细胞消除了圣草酚诱导的 HO-1 和 γ-GCS 表达及其保护作用。总之，这些结果表明圣草酚通过激活 Nrf2/ARE 途径上调 HO-1 和 γ-GCS 表达，并保护 PC12 细胞免受 H2O2 诱导的氧化应激。 (C) 2012 Elsevier Ltd. 保留所有权利。
Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre has long been established as an antioxidant. The present study was designed to explore the protective effects of eriodictyol against hydrogen peroxide (H2O2)-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, differentiated PC12 cells were cultured and exposed to 200 mu M H2O2 in the absence or presence of eriodictyol (20, 40 and 80 mu M). In addition, the potential contribution of the Nrf2/ARE neuroprotective pathway in eriodictyol-mediated protection against H2O2-induced neurotoxicity was also investigated. The results showed that H2O2-induced cell death can be inhibited in the presence of eriodictyol as measured by assays for MIT and apoptosis. Further study revealed that eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of home oxygenase (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS), and increased the levels of intracellular glutathione. Treatment of PC12 cells with Nrf2 small interference RNA abolished eriodictyol-induced HO-1 and gamma-GCS expression and its protective effects. In conclusion, these results suggest that eriodictyol upregulates HO-1 and gamma-GCS expression through the activation of Nrf2/ARE pathway and protects PC12 cells against H2O2-induced oxidative stress. (C) 2012 Elsevier Ltd. All rights reserved.