Changes in the Mitochondrial Subproteome of Mouse Brain Rpn13-Binding Proteins Induced by the Neurotoxin MPTP and the Neuroprotector Isatin

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2021-08-16 DOI:10.1134/S1990750821030021

O. A. Buneeva, A. T. Kopylov, O. V. Gnedenko, M. V. Medvedeva, I. G. Kapitsa, E. A. Ivanova, A. S. Ivanov, A. E. Medvedev

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引用次数: 1

Abstract—

Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson’s disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle plays an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al., Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, (2020), vol. 14, pp. 297−305). In this study we have investigated the effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the neuroprotector isatin on the mitochondrial subproteome of Rpn13-binding proteins of the mouse brain. Administration of MPTP (30 mg/kg) to animals caused movement disorders typical of PD, while pretreatment with isatin (100 mg/kg, 30 min before MPTP) reduced their severity. At the same time, the injection of MPTP, isatin, or their combination (isatin + MPTP) had a significant impact on the total number and the composition of Rpn13-binding proteins. The injection of MPTP decreased the total number of Rpn13-binding proteins in comparison with control, and the injection of isatin prior to MPTP or without MPTP caused an essential increase in the number of Rpn13-binding proteins, mainly of the functional group of proteins participating in the protein metabolism regulation, gene expression, and cell division and differentiation. Selected biosensor validation confirmed the interaction of the proteasome Rpn13 subunit with some proteins (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, histones H2A and H2B) recognized during proteomic profiling. The results obtained suggest that under the conditions of experimental MPTP-induced parkinsonism the neuroprotective effect of isatin may be aimed at the interaction of mitochondria with the components of UPS.

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神经毒素MPTP和神经保护剂Isatin诱导小鼠脑rpn13结合蛋白线粒体亚蛋白质组的变化

线粒体功能障碍和泛素-蛋白酶体系统(UPS)功能衰竭是帕金森病(PD)发展的重要因素。位于调控亚粒子(19S)上的蛋白酶体亚基Rpn13在将降解的蛋白质传递到蛋白酶体的蛋白水解(20S)部分中起重要作用。我们之前已经发现了几种与Rpn13特异性结合的脑线粒体蛋白(Buneeva等人，Biochemistry (Moscow)， Supplement Series B: Biomedical Chemistry， (2020)， vol. 14, pp. 297−305)。在本研究中，我们研究了神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)和神经保护剂isatin对小鼠脑rpn13结合蛋白线粒体亚蛋白质组的影响。MPTP (30 mg/kg)给药可引起PD典型的运动障碍，而isatin预处理(100 mg/kg, MPTP前30分钟)可减轻其严重程度。同时，注射MPTP、isatin或它们的组合(isatin + MPTP)对rpn13结合蛋白的总数和组成有显著影响。与对照组相比，注射MPTP减少了rpn13结合蛋白的总数，而在MPTP之前或未注射isatin导致rpn13结合蛋白的数量明显增加，主要是参与蛋白质代谢调节、基因表达和细胞分裂分化的功能蛋白群。选定的生物传感器验证证实了蛋白酶体Rpn13亚基与蛋白质组学分析中识别的一些蛋白质(甘油醛-3-磷酸脱氢酶、丙酮酸激酶、组蛋白H2A和H2B)的相互作用。结果提示，在实验性mptp诱导的帕金森病条件下，isatin的神经保护作用可能是针对线粒体与UPS成分的相互作用。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.