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Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo
Translational Neurodegeneration ( IF 10.8 ) Pub Date : 2018-08-17 , DOI: 10.1186/s40035-018-0125-9
Ming-Shu Mo 1 , Gui-Hua Li 1 , Cong-Cong Sun 2 , Shu-Xuan Huang 1 , Lei Wei 1 , Li-Min Zhang 3 , Miao-Miao Zhou 1 , Zhuo-Hua Wu 1 , Wen-Yuan Guo 1 , Xin-Ling Yang 4 , Chao-Jun Chen 5 , Shao-Gang Qu 6 , Jian-Xing He 7 , Ping-Yi Xu 1, 4
Affiliation  

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. In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. 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. Taken together, our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

中文翻译:

多巴胺能神经元在体外和体内显示由 6-羟基多巴胺诱导的低分子量蛋白 7 活性增加

主要组织相容性复合物 I 类 (MHC-I) 的异常表达在帕金森病 (PD) 的黑质 (SN) 中的多巴胺能 (DA) 神经元中增加。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 通路。在这项研究中,我们在体外和体内使用 6-羟基多巴胺 (6-OHDA) 模型研究了 β5i 在 DA 神经元中的作用。我们发现 6-OHDA 以浓度和时间依赖性方式上调 DA 神经元中的 β5i 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 神经元中的 6-OHDA 神经毒性。β5i 的抑制进一步促进了由 6-OHDA 诱导的 Caspase 3 相关通路的激活。β5i 还激活与抗原处理 1 (TAP1) 相关的转运蛋白并促进 DA 神经元上的 MHC-I 表达。总之,我们的数据表明β5i 在 6-OHDA 治疗下在 DA 神经元中被激活,并且可能在 PD 中发挥神经保护作用。
更新日期:2018-08-17
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