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The Effect of a Neuroprotective Dose of Isatin or Deprenyl to Mice on the Profile of Brain Isatin-Binding Proteins

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Abstract—

Isatin (indol-2,3-dione) is an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals. It exhibits a wide range of biological and pharmacological activities realized via interaction with numerous isatin-binding proteins, which have been identified during proteomic profiling of mouse and rat brain preparations. Some of these proteins are involved in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl (selegiline), a selective mechanism-based inhibitor of monoamine oxidase B (MAO B) and a pharmacological agent used for treatment of Parkinson’s disease. In this study, we have investigated the effect of a single dose administration of isatin (100 mg/kg) and deprenyl (10 mg/kg) to mice on the profile of the brain isatin-binding proteins. Comparative proteomic analysis of brain isatin-binding proteins of mice treated with isatin or deprenyl resulted in identification of a representative group of proteins (n = 200) sensitive to the administration of these substances. The change in the profile of isatin-binding proteins may be obviously attributed to accumulation of isatin and deprenyl in the brain and their interaction with target proteins; this prevents protein binding to the affinity sorbent. In this context, the identified brain isatin-binding proteins of the control animals obviously represent specific targets that interact directly with isatin (and also with deprenyl) in vivo. Isatin or deprenyl administered to animals interact with these proteins and thus prevent their binding to the affinity sorbent (the immobilized isatin analogue).

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ACKNOWLEDGMENTS

Mass spectrometric analysis of proteins was performed in the Center of Collective Use “Human Proteome” at the Institute of Biomedical Chemistry (Moscow).

Funding

This work performed within the framework of the State Academies of Sciences Fundamental Scientific Research Program for 2013−2020 (mass spectrometry analysis) was partially supported by the Russian Foundation for Basic Research (project no. 18-015-00042; the study of the effect of isatin and deprenyl on animals and sample preparation for mass spectrometric analysis).

Supplementary materials are available in electronic version of the article on the journal website (pbmc.ibmc.msk.ru).

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Correspondence to A. E. Medvedev.

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The experiments were carried out in compliance with generally accepted norms of the humane care of laboratory animals. Authors declare that they have no conflict of inte-rest.

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Translated by A. Medvedev

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Buneeva, O.A., Kapitsa, I.G., Ivanova, E.A. et al. The Effect of a Neuroprotective Dose of Isatin or Deprenyl to Mice on the Profile of Brain Isatin-Binding Proteins. Biochem. Moscow Suppl. Ser. B 14, 116–126 (2020). https://doi.org/10.1134/S1990750820020031

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