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多巴胺能神经元在体外和体内均表现出由6-羟基多巴胺诱导的低分子量蛋白7活性增加。

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo.

作者信息

Mo Ming-Shu, Li Gui-Hua, Sun Cong-Cong, Huang Shu-Xuan, Wei Lei, Zhang Li-Min, Zhou Miao-Miao, Wu Zhuo-Hua, Guo Wen-Yuan, Yang Xin-Ling, Chen Chao-Jun, Qu Shao-Gang, He Jian-Xing, Xu Ping-Yi

机构信息

1Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120 Guangdong China.

2Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012 Shandong China.

出版信息

Transl Neurodegener. 2018 Aug 17;7:19. doi: 10.1186/s40035-018-0125-9. eCollection 2018.

DOI:10.1186/s40035-018-0125-9
PMID:30128145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6097308/
Abstract

BACKGROUND

Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells.

METHODS

In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and .

RESULTS

We showed that 6-OHDA upregulated β5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of β5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of β5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA β5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons.

CONCLUSION

Taken together, our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

摘要

背景

帕金森病（PD）患者黑质（SN）中多巴胺能（DA）神经元的主要组织相容性复合体I类（MHC-I）异常表达增加。低分子量蛋白7（β5i）是免疫蛋白酶体的蛋白水解亚基，可调节免疫细胞中的蛋白质降解和MHC途径。

方法

在本研究中，我们使用体外6-羟基多巴胺（6-OHDA）模型研究了β5i在DA神经元中的作用。

结果

我们发现6-OHDA以浓度和时间依赖性方式上调DA神经元中β5i的表达。β5i的抑制和下调诱导了葡萄糖调节蛋白（Bip）的表达，并加剧了DA神经元中6-OHDA的神经毒性。β5i的抑制进一步促进了6-OHDA诱导的Caspase 3相关途径的激活。β5i还激活了与抗原加工相关的转运体1（TAP1），并促进了DA神经元上MHC-I的表达。

结论

综上所述，我们的数据表明β5i在6-OHDA处理下在DA神经元中被激活，并可能在PD中发挥神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/19ce550fc4fd/40035_2018_125_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/b193a963f449/40035_2018_125_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/91dabc31a194/40035_2018_125_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/4b0fcd8d0c56/40035_2018_125_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/57dd27f390be/40035_2018_125_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/7bd4e635237d/40035_2018_125_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/19ce550fc4fd/40035_2018_125_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/b193a963f449/40035_2018_125_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/91dabc31a194/40035_2018_125_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/4b0fcd8d0c56/40035_2018_125_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/57dd27f390be/40035_2018_125_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/7bd4e635237d/40035_2018_125_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f09d/6097308/19ce550fc4fd/40035_2018_125_Fig6_HTML.jpg

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