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. 2017 Jul;63(4):316-320.
doi: 10.18097/PBMC20176304316.

[The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins]

[Article in Russian]
O A Buneeva  1 , A T Kopylov  1 , L N Nerobkova  2 , I G Kapitsa  2 , V G Zgoda  1 , A E Medvedev  1
Affiliations

[The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins]

[Article in Russian]
O A Buneeva et al. Biomed Khim. 2017 Jul.

Abstract
in English, Russian

Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins. The aim of this study was to investigate the profile of brain isatin-binding proteins in mice with MPTP-induced Parkinsonism (90 min and seven days after administration of this neurotoxin). A single dose administration of MPTP (30 mg/kg, ip.) was accompanied by locomotor impairments in the open field test 90 min after administration; seven days after MPTP administration locomotor activity of mice significantly improved but did not reach the control level. Five independent experiments on proteomic profiling of isatin-binding proteins resulted in confident identification of 96±12 proteins. Development of MPTP-induced locomotor impairments was accompanied by a significant decrease in the number of isatin-binding proteins (63±6; n=5; p<0.01). Seven days after MPTP administration the total number of identified proteins increased and reached the control level (132±34; n=4). The profiles of isatin-binding proteins were rather specific for each group of mice: in the control group these proteins (which were not found in both groups of MPTP-treated mice) represented more than 70% of total proteins. In the case of MPTP treated mice this parameter was 60% (90 min after MPTP administration) and >82% (seven days after MPTP administration). The major changes were found in the groups of isatin-binding proteins involved into cytoskeleton formation and exocytosis, regulation of gene expression, cell division and differentiation and also proteins involved in signal transduction.

Izatin (indol-2,3-dion) – éndogennyĭ indol, obnaruzhennyĭ v mozge, perifericheskikh tkaniakh i biologicheskikh zhidkostiakh mlekopitaiushchikh. On okazyvaet neĭroprotektornoe deĭstvie, snizhaia vyrazhennost' dvigatel'nykh narusheniĭ u zhivotnykh pri modelirovanii bolezni Parkinsona. Proiavliaia shirokiĭ spektr biologicheskoĭ aktivnosti, izatin vzaimodeĭstvuet s mnogochislennymi izatin-sviazyvaiushchimi belkami. Tsel'iu dannogo issledovaniia bylo izuchit' profil' izatin-sviazyvaiushchikh belkov mozga mysheĭ s MFTP-indutsirovannym parkinsonizmom na vysote razvitiia dvigatel'nykh narusheniĭ (cherez 90 min) i cherez sem' dneĭ posle vvedeniia étogo neĭrotoksina. Odnokratnoe vvedenie MFTP (30 mg/kg, v/br.) privodilo k razvitiiu dvigatel'nykh rasstroĭstv v teste “otkrytoe pole”; cherez sem' dneĭ posle vvedeniia MFTP dvigatel'naia aktivnost' zhivotnykh uluchshalas', no urovnia kontrol'nykh zhivotnykh ne dostigala. V khode piati nezavisimykh éksperimentov po proteomnomu profilirovaniiu izatin-sviazyvaiushchikh belkov mozga kontrol'nykh zhivotnykh bylo identifitsirovano 96±12 belkov. Na vysote dvigatel'nykh narusheniĭ, vyzvannykh vvedeniem MFTP, chislo izatin-sviazyvaiushchikh belkov sushchestvenno snizilos' (63±6; n=5; p<0,01). Cherez sem' dneĭ posle vvedeniia MFTP obshchee chislo izatin-sviazyvaiushchikh belkov uvelichilos', dostignuv urovnia kontrolia (132±34; n=4). Profili izatin-sviazyvaiushchikh belkov byli spetsifichny dlia kazhdoĭ gruppy mysheĭ: v kontrole éti belki (kotorye ne byli obnaruzheny ni na vysote dvigatel'nykh narusheniĭ, ni cherez nedeliu posle vvedeniia MFTP) sostavili bolee 70% ot obshchego chisla identifitsirovannykh belkov. Dlia mysheĭ, poluchavshikh in"ektsiiu MFTP, na vysote dvigatel'nykh narusheniĭ étot pokazatel' sostavil okolo 60%, a cherez sem' dneĭ posle vvedeniia MFTP >82%. Osnovnye izmeneniia obnaruzheny v gruppakh izatin-sviazyvaiushchikh belkov, uchastvuiushchikh v obrazovanii tsitoskeleta i ékzotsitoze, belkov, reguliruiushchikh protsessy ékspressii genov, kletochnogo deleniia i differentsirovki, a takzhe belkov, vovlechennykh v signal'nuiu transduktsiiu.

Keywords: MPTP-induced Parkinsonism; brain; isatin; isatin-binding proteins; proteomic profiling.

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