Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1

• DOI: 10.1016/j.toxlet.2010.06.023
• Publication Date: 2010-07-07T08:36:37Z
• Authors: Chunshu Hao; Wei Liu; Xiaofei Luan; Yang Li; Haiyan Gui; Yan Peng; Jianping Shen; Gang Hu; Jian Yang
• Keywords: Aquaporin 4; Lipopolysaccharides; Mice, Knockout; 0301 basic medicine; 1-Methyl-4-phenylpyridinium; 0303 health sciences; Ethanol; Cell Survival; Reverse Transcriptase Polymerase Chain Reaction; Brain; Cytochrome P-450 CYP2E1; Immunohistochemistry; Up-Regulation; Cytochrome P-450 CYP2E1 Inhibitors; Mice; 03 medical and health sciences; Astrocytes; Animals; Reactive Oxygen Species; Cells, Cultured

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.