Corilagin prevents tert-butyl hydroperoxide-induced oxidative stress injury in cultured N9 murine microglia cells
Corilagin prevents tert-butyl hydroperoxide-induced oxidative stress injury in cultured N9 murine microglia cells
复制标题
DOI：
10.1016/j.neuint.2011.05.020
复制
发表时间：
2011-08-01
影响因子：
4.2
通讯作者：
Chen, Chonghong
中科院分区：
文献类型：
--
作者：
Chen, Yiyan;Chen, Chonghong
氧化应激在神经退行性疾病中起重要作用。活性氧介导的体内小胶质细胞应激可导致细胞损伤，并优先诱导神经元损伤。柯里拉京是酚类单宁家族的新成员，具有抗氧化特性。在这项研究中，我们研究了柯里拉京对叔丁基过氧化氢（TBHP）诱导的损伤在培养的N9小鼠小胶质细胞的影响和潜在的机制，通过甲基四氮唑测定和氧化损伤测定。我们发现N9细胞暴露于TBHP诱导细胞毒性，如细胞收缩、细胞活力丧失、乳酸脱氢酶（LDH）泄漏增加和细胞内ROS水平增加所证明的。与此相反，TBHP降低超氧化物歧化酶活性和总细胞抗氧化能力，但谷胱甘肽没有减少。此外，TBHP处理与线粒体膜电位的损失，并通过神经细胞介导的途径诱导细胞凋亡，涉及下调Bcl-2的表达和上调Bax/Bcl-2的比例。有趣的是，用柯里拉京预处理逆转了这些反应。这些数据共同表明，柯里拉京可以减轻TBHP诱导的氧化应激损伤的小胶质细胞，其保护作用可能归因于其抗氧化和抗凋亡特性。我们的研究结果表明，corilagin应该是一个潜在的候选人，用于治疗氧化应激诱导的神经退行性疾病。(C)2011 Elsevier B. V.保留所有权利。
Oxidative stress plays an important role in neurodegenerative diseases. Reactive oxygen species (ROS)-mediated stress in microglia in vivo could result in cellular injuries and preferentially induces neuronal injury. Corilagin, a novel member of the phenolic tannin family, has been shown to possess antioxidant properties. In this study, we investigated the effects of corilagin on tert-butyl hydroperoxide (TBHP)-induced injury in cultured N9 murine microglial cells and the underlying mechanisms by a methyltetrazolium assay and oxidative damage assay. We found that exposure of N9 cells to TBHP induced cytotoxicity as demonstrated by cell shrinkage, loss of cell viability, increased lactate dehydrogenase (LDH) leakage, and increased intracellular levels of ROS. By contrast, TBHP reduced both superoxide dismutase activity and total cell anti-oxidation capacity, but glutathione was not reduced. Moreover, TBHP treatment was associated with the loss of mitochondrial membrane potential, and it induced cell apoptosis through the mitochondrial-mediated pathway involving the down-regulation of Bcl-2 expression and up-regulation of the Bax/Bcl-2 ratio. Interestingly, pre-treatment with corilagin reversed these reactions. These data collectively indicated that corilagin could attenuate TBHP-induced oxidative stress injury in microglial cells, and its protective effects may be ascribed to its antioxidant and antiapoptotic properties. Our findings suggest that corilagin should be a potential candidate for the treatment of oxidative stress-induced neurodegenerative diseases. (C) 2011 Elsevier B.V. All rights reserved.