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通过调控通路促进帕金森病。

Promotes Parkinson's Disease via Modulating Pathway.

机构信息

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Endocrine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

出版信息

Hum Gene Ther. 2020 Dec;31(23-24):1274-1287. doi: 10.1089/hum.2020.106. Epub 2020 Oct 15.

DOI:10.1089/hum.2020.106
PMID:32808542
Abstract

taurine upregulated gene 1 () participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP) and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) . The expressions of , , phosphatase and tensin homologue (), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between and was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, expression was upregulated and that of was downregulated. Further research showed that sponged and regulated expression. Silencing of not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation , pathological damage and neuroinflammation , but also suppressed the expressions of and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the inhibitor. Thus, knocking down might have a protective effect on PD through the pathway.

摘要

牛磺酸上调基因 1 () 参与神经系统疾病,但在帕金森病 (PD) 中的作用尚不清楚。本研究探讨了在 PD 中的功能和机制。通过 1-甲基-4-苯基吡啶 (MPP) 诱导的 SH-SY5Y 细胞和 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 处理的小鼠构建 PD 模型。通过定量逆转录-PCR 和 Western blot 测定 、 、磷酸酶张力蛋白同源物 ()、酪氨酸羟化酶 (TH) 和 Bcl-2 的表达以及 cleaved caspase-3 的表达。通过商业试剂盒检测 SH-SY5Y 细胞和黑质组织的活力、凋亡、活性氧和炎症因子的释放。通过双荧光素酶报告基因测定分析 与 的相互作用。通过苏木精/伊红和免疫组织化学染色评估病理损伤和 TH 阳性细胞的比例。在 PD 细胞模型和小鼠模型中, 表达上调, 表达下调。进一步的研究表明, 可海绵吸附并调节 的表达。沉默 不仅可以保护 SH-SY5Y 细胞免受细胞凋亡、氧化应激和神经炎症的影响,还可以抑制 MPP 处理的 SH-SY5Y 细胞中 和 cleaved caspase-3 的表达,增加 TH 和 Bcl-2 的表达。然而,siTUG1 在 SH-SY5Y 细胞中的保护作用被 抑制剂显著抑制。因此,敲低 可能通过 途径对 PD 具有保护作用。

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