Wnt1 Promotes EAAT2 Expression and Mediates the Protective Effects of Astrocytes on Dopaminergic Cells in Parkinson's Disease
Copyright © 2019 Lei Wei et al.
Veröffentlicht in: | Neural plasticity. - 1998. - 2019(2019) vom: 24., Seite 1247276 |
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1. Verfasser: | |
Weitere Verfasser: | , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2019
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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 |
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 |
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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 |