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

Authors :
Ming-Shu Mo
Gui-Hua Li
Cong-Cong Sun
Shu-Xuan Huang
Lei Wei
Li-Min Zhang
Miao-Miao Zhou
Zhuo-Hua Wu
Wen-Yuan Guo
Xin-Ling Yang
Chao-Jun Chen
Shao-Gang Qu
Jian-Xing He
Ping-Yi Xu
Source :
Translational Neurodegeneration, Vol 7, Iss 1, Pp 1-12 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

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 vivo. 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.

Details

Language :
English
ISSN :
20479158
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Translational Neurodegeneration
Publication Type :
Academic Journal
Accession number :
edsdoj.4c3047ad567c4e499f5b97fbfed25112
Document Type :
article
Full Text :
https://doi.org/10.1186/s40035-018-0125-9