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The Effect of Neurotoxin MPTP Administration to Mice on the Proteomic Profile of Brain Isatin-Binding Proteins

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Abstract

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 characterized by maximal manifestation of locomotor impairments (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 MPTPinduced 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.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow, 119121, Russia

    O. A. Buneeva, A. T. Kopylov, V. G. Zgoda & A. E. Medvedev

  2. Zakusov Institute of Pharmacology, ul. Baltiyskaya 8, Moscow, 125315, Russia

    L. N. Nerobkova & I. G. Kapitsa

Authors
  1. O. A. Buneeva
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  2. A. T. Kopylov
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  3. L. N. Nerobkova
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  4. I. G. Kapitsa
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  5. V. G. Zgoda
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  6. A. E. Medvedev
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Correspondence to A. E. Medvedev.

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Original Russian Text © O.A. Buneeva, A.T. Kopylov, L.N. Nerobkova, I.G. Kapitsa, V.G. Zgoda, A.E. Medvedev, 2018, published in Biomeditsinskaya Khimiya.

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The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins, Biomeditsinskaya khimiya

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Buneeva, O.A., Kopylov, A.T., Nerobkova, L.N. et al. The Effect of Neurotoxin MPTP Administration to Mice on the Proteomic Profile of Brain Isatin-Binding Proteins. Biochem. Moscow Suppl. Ser. B 12, 22–26 (2018). https://doi.org/10.1134/S1990750818010043

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  • DOI: https://doi.org/10.1134/S1990750818010043

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