title: Aquaporin-4 mediates astrocyte response to β-amyloid.
abstract: It has been demonstrated that the water channel protein aquaporin-4 (AQP4) plays an important role in astrocyte plasticity in response to a variety of injuries or stimuli. However, the potential role of AQP4 in astrocyte response to β-amyloid (Aβ) has not been studied. The purpose of this study was to investigate this issue. Compared to media control, the lower concentrations of Aβ(1-42) (0.1-1 μM) increased AQP4 expression in cultured mouse cortical astrocytes, while the higher concentrations of Aβ(1-42) (10 μM) decreased AQP4 expression. AQP4 gene knockout reduced Aβ(1-42)-induced astrocyte activation and apoptosis, which was associated with a reduction in the uptake of Aβ via decreased upregulation of low-density lipoprotein receptor related protein-1. Moreover, time-course and levels of Aβ(1-42)-induced mitogen-activated protein kinase phosphorylation were altered in AQP4 null astrocytes compared with wild-type controls. Our data reveal a novel role of AQP4 in the uptake of Aβ by astrocytes, indicating that AQP4 is a molecular target for Alzheimer's disease.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu Province 210029, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Chan
authors.initials: C
authors.lastname: Yuan
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.forename: Minxia
authors.initials: M
authors.lastname: Gu
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout
chemical_list: D016229:Amyloid beta-Peptides; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4