Brain mitochondrial subproteome of Rpn10-binding proteins and its changes induced by the neurotoxin MPTP and the neuroprotector isatin
- 作者: Medvedev A.1, Buneeva O.1, Kopylov A.1, Tikhonova O.1, Medvedeva M.2, Nerobkova L.3, Kapitsa I.3, Zgoda V.1
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隶属关系:
- Institute of Biomedical Chemistry
- Biological Faculty
- Zakusov Institute of Pharmacology
- 期: 卷 82, 编号 3 (2017)
- 页面: 330-339
- 栏目: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151295
- DOI: https://doi.org/10.1134/S0006297917030117
- ID: 151295
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详细
Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson’s disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS. The 19S proteasomal Rpn10 subunit is considered as a ubiquitin receptor responsible for delivery of ubiquitinated proteins to the proteasome proteolytic machinery. In this study, we investigated proteomic profiles of mouse brain mitochondrial Rpn10-binding proteins, brain monoamine oxidase B (MAO B) activity, and their changes induced by a single-dose administration of the neurotoxin MPTP and the neuroprotector isatin. Administration of isatin to mice prevented MPTP-induced inactivation of MAO B and influenced the profile of brain mitochondrial Rpn10-binding proteins, in which two pools of proteins were clearly recognized. The constitutive pool was insensitive to neurotoxic/neuroprotective treatments, while the variable pool was specifically influenced by MPTP and the neuroprotector isatin. Taking into consideration that the neuroprotective dose of isatin used in this study can result in brain isatin concentrations that are proapoptotic for cells in vitro, the altered repertoire of mitochondrial Rpn10-binding proteins may thus represent a part of a switch mechanism from targeted elimination of individual (damaged) proteins to more efficient (“global”) elimination of damaged organelles and whole damaged cells.
作者简介
A. Medvedev
Institute of Biomedical Chemistry
编辑信件的主要联系方式.
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119121
O. Buneeva
Institute of Biomedical Chemistry
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119121
A. Kopylov
Institute of Biomedical Chemistry
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119121
O. Tikhonova
Institute of Biomedical Chemistry
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119121
M. Medvedeva
Biological Faculty
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119991
L. Nerobkova
Zakusov Institute of Pharmacology
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 125315
I. Kapitsa
Zakusov Institute of Pharmacology
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 125315
V. Zgoda
Institute of Biomedical Chemistry
Email: professor57@yandex.ru
俄罗斯联邦, Moscow, 119121