التفاصيل البيبلوغرافية
| العنوان: |
Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. |
| المؤلفون: |
Xiao-Long Sun, Bei-Yu Chen, Hai-Kang Zhao, Ying-Ying Cheng, Min-Hua Zheng, Li Duan, Wen Jiang, Liang-Wei Chen, Sun, Xiao-Long, Chen, Bei-Yu, Zhao, Hai-Kang, Cheng, Ying-Ying, Zheng, Min-Hua, Duan, Li, Jiang, Wen, Chen, Liang-Wei |
| المصدر: |
Journal of Neuroinflammation; 7/8/2016, Vol. 13, p1-14, 14p |
| مصطلحات موضوعية: |
GLIOSIS, PARKINSON'S disease patients, TUMOR growth, TUMOR suppressor genes, ONCOGENES |
| مستخلص: |
Background: Reactive astrogliosis is a remarkable pathogenetic hallmark of the brains of Parkinson's disease (PD) patients, but its progressive fate and regulation mechanisms are poorly understood. In this study, growth arrest specific 1 (Gas1), a tumor growth suppressor oncogene, was identified as a novel modulator of the cell apoptosis of reactive astrocytes in primary culture and the injured substantia nigra.Methods: Animal models and cell cultures were utilized in the present study. Lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated animal models were used to detect Gas1 expression in the brain via immunohistochemistry and western blot. Cell cultures were performed to analyze Gas1 functions in the viability and apoptosis of reactive astrocytes and SH-SY5Y cells by double labeling, CCK-8, LDH, TUNEL, flow cytometry, and siRNA knockdown methods.Results: Gas1 expressions were significantly elevated in the majority of the reactive astrocytes of the brains with LPS or MPTP insults. In the injured substantia nigras, GFAP-positive astrocytes exhibited higher levels of cleaved caspase-3. In cell culture, the up-regulated Gas1 expression induced apoptosis of reactive astrocytes that were insulted by LPS in combination with interferon-γ and tumor necrosis factor-a. This effect was confirmed through siRNA knockdown of Gas1 gene expression. Finally and interestingly, the potential underlying signaling pathways were evidently related to an increase in the Bax/Bcl-2 ratio, the abundant generation of reactive oxygen species and the activation of cleaved caspase-3.Conclusions: This study demonstrated that the up-regulation of inducible Gas1 contributed to the apoptosis of reactive astrocytes in the injured nigra. Gas1 signaling may function as a novel regulator of astrogliosis and is thus a potential intervention target for inflammatory events in PD conditions. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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