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

Autor: Lei Wei, Miaomiao Zhou, Jian-Xing He, Guihua Li, Xinling Yang, Chaojun Chen, Shuxuan Huang, Shaogang Qu, Zhuo-Hua Wu, Wenyuan Guo, Cong-Cong Sun, Limin Zhang, Ping-Yi Xu, Mingshu Mo
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Translational Neurodegeneration, Vol 7, Iss 1, Pp 1-12 (2018)
Translational Neurodegeneration
ISSN: 2047-9158
DOI: 10.1186/s40035-018-0125-9
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s40035-018-0125-9) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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