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

• Published in: Neural plasticity Vol. 2019; no. 2019; pp. 1 - 12
• Main Authors: Xu, Pingyi, Lu, Zhengqi, Dai, Yongqiang, Li, Haiyan, Lu, Zhenze, Zou, Jing, Mo, Mingshu, Ding, Li, Chen, Chuan, Wei, Lei, Wu, Haotian
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; Hindawi Limited
• Subjects: Antibodies; Apoptosis; Dopamine; Flow cytometry; Gene expression; Kinases; Neurodegeneration; Neurons; Parkinson's disease; Pathogenesis; Proteins; Signal transduction; United Kingdom > UK; United States > US; China; Japan
• ISSN: 2090-5904; 1687-5443
• DOI: 10.1155/2019/1247276

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.