Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1.
Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1.
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Aquaporin-4 敲除通过增加细胞色素 P4502E1 的表达来增强 1-甲基-4-苯基吡啶鎓离子和脂多糖诱导的星形胶质细胞毒性。
DOI：
10.1016/j.toxlet.2010.06.023
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发表时间：
2010-10-05
影响因子：
3.5
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Hao, Chunshu;Liu, Wei;Luan, Xiaofei;Li, Yang;Gui, Haiyan;Peng, Yan;Shen, Jianping;Hu, Gang;Yang, Jian
水通道蛋白-4(AQP4)在星形胶质细胞功能调节中的作用已被广泛研究。然而，关于其对药物代谢酶如细胞色素P4502E1的贡献的信息很少。本研究通过调节星形胶质细胞中细胞色素P450 2的表达，探讨AQP4是否参与了MPP+和内毒素引起的细胞损伤过程。与野生型相比，在原代星形胶质细胞中，AQP4基因敲除增加了MPP+、内毒素和乙醇诱导的细胞损伤和活性氧(ROS)的产生。值得注意的是，AQP4基因敲除增强了暴露于MPP+、内毒素和乙醇的星形胶质细胞中CYP2E1的表达上调。此外，二烯丙基硫化物(DAS)可部分或几乎阻断MPP+和脂多糖诱导的星形胶质细胞损伤和ROS的产生。这些结果表明，AQP4通过降低ROS的产生与细胞色素P4502的表达减少来保护星形胶质细胞免受MPP+和内毒素的损伤。
The role of aquaporin-4 (AQP4) in the regulation of astrocytes function has been widely investigated. However, there is little information about its contribution to the drug metabolism enzymes such as Cytochrome P4502E1. In the present study, we investigated whether AQP4 is involved in the process of the cell damage caused by MPP+ and LPS through regulating the expression of CYP2E1 in astrocytes. Compared to the wild-type, in primary astrocytes, AQP4 knockout increased the cell damage and the reactive oxygen species (ROS) production which were induced by MPP+, LPS and ethanol. Notably, AQP4 knockout enhanced the up-regulation of the expression of CYP2E1 in astrocytes exposed to MPP+, LPS and ethanol. Furthermore, Diallylsulphide (DAS), a CYP2E1 inhibitor, partially or almost abolished the cell injury and the ROS production of the astrocytes induced by MPP+ and LPS. These findings indicate AQP4 protects astrocytes from the damage caused by MPP+ and LPS through reducing the ROS production correlation to the diminished expression of CYP2E1.
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