title: Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1.
abstract: 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.
authors.affiliation: Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Chunshu
authors.initials: C
authors.lastname: Hao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Luan
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gui
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Jianping
authors.initials: J
authors.lastname: Shen
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D000431:Ethanol / Q000633:toxicity; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D015655:1-Methyl-4-phenylpyridinium