Wnt1 Promotes EAAT2 Expression and Mediates the Protective Effects of Astrocytes on Dopaminergic Cells in Parkinson's Disease

Copyright © 2019 Lei Wei et al.

Bibliographische Detailangaben
Veröffentlicht in:Neural plasticity. - 1998. - 2019(2019) vom: 24., Seite 1247276
1. Verfasser: Wei, Lei (VerfasserIn)
Weitere Verfasser: Chen, Chuan, Ding, Li, Mo, Mingshu, Zou, Jing, Lu, Zhenze, Li, Haiyan, Wu, Haotian, Dai, Yongqiang, Xu, Pingyi, Lu, Zhengqi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Neural plasticity
Schlagworte:Journal Article Research Support, Non-U.S. Gov't CTNNB1 protein, human Excitatory Amino Acid Transporter 2 Wnt1 Protein beta Catenin Glutamic Acid 3KX376GY7L Oxidopamine 8HW4YBZ748
Beschreibung
Zusammenfassung:Copyright © 2019 Lei Wei et al.
Background: Wnt/β-catenin signaling has been reported to exert cytoprotective effects in a cellular model of Parkinson's disease (PD). Glutamate excitotoxicity has been suggested to contribute to the pathogenesis of PD, and excitatory amino acid transporters (EAATs) play a predominant role in clearing excessive glutamate. EAAT2 is mainly expressed in astrocytes, which are an important source of Wnt signaling in the brain
Methods: Wnt1-overexpressing U251 astrocytes were indirectly cocultured with dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Cell toxicity was determined by cell viability and flow cytometric detection. Glutamate level in the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression of Wnt1, β-catenin, and EAAT2. Immunofluorescence was used to display the expression and translocation of NF-κB p65
Results: 6-OHDA treatment significantly decreased cell viability in both U251 cells and SH-SY5Y cells, inhibited the expression of Wnt1, β-catenin, and EAAT2 in U251 cells, and increased the glutamate level in the culture medium. Coculture with Wnt1-overexpressing U251 cells attenuated 6-OHDA-induced apoptosis in SH-SY5Y cells. Overexpression of Wnt1 decreased the glutamate level in the culture media, upregulated β-catenin, EAAT2, and NF-κB levels, and promoted the translocation of NF-κB from the cytoplasm to the nucleus in U251 cells
Conclusion: Wnt1 promoted EAAT2 expression and mediated the cytoprotective effects of astrocytes on dopaminergic cells. NF-κB might be involved in the regulation of EAAT2 by Wnt1
Beschreibung:Date Completed 27.07.2020
Date Revised 27.07.2020
published: Electronic-eCollection
Citation Status MEDLINE
ISSN:1687-5443
DOI:10.1155/2019/1247276