The Effect of Deprenyl and Isatin Administration to Mice on the Proteomic Profile of Liver Isatin-Binding Proteins
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Isatin (indol-2,3-dione) is an endogenous indole found in the brain, peripheral tissues and biological body fluids of humans and animals. Its wide spectrum of biological activity is realized via interaction with numerous isatin-binding proteins; these include proteins playing an important role in the development of neurodegenerative pathology. In the context of the neuroprotective effect, the effect of isatin is comparable to the effects of deprenyl, a pharmacological agent used for treatment of Parkinson’s disease. In this study, the effects of the course of deprenyl (1 mg/kg) and isatin (20 mg/kg) administration for 21 days on the profile of the isatin-binding proteins of the liver of mice have been investigated. Proteomic profiling of liver isatin-binding proteins of control mice by means of 5-aminocaproylisatin as an affinity ligand resulted in identification of 105 proteins. Treatment of animals with a low dose of isatin slightly decreased (up to 91), while injections of deprenyl slightly increased (up to 120) the total number of isatin-binding proteins. 75 proteins were common for all three groups; they represented from 62.5% (in deprenyl treated mice) and 71% (in control mice), to 82% (isatin treated mice) of the total number of identified liver isatin-binding proteins. The proteomic analysis of the isatin-binding proteins of mice treated with isatin (20 mg/kg) or deprenyl (1 mg/kg) for 21 days revealed a representative group of proteins (n = 30) that were sensitive to the administration of these compounds. Taking into consideration the previously obtained results, it is reasonable to suggest that the change in the profile of isatin-binding proteins may be attributed to accumulation of isatin and deprenyl in the liver and interaction with target proteins prevents their subsequent binding to the affinity sorbent. In this context, the identified isatin-binding liver proteins of control animals that do not bind to the affinity sorbent (immobilized isatin analogue) after treatment of animals with either deprenyl or isatin appear to be specific targets directly interacting with isatin in vivo.
Keywords:isatin deprenyl isatin-binding proteins mouse liver proteomic profiling
This work was performed within the framework of the Program for Basic Research of State Academies of Sciences for 2013–2020 and was partially supported by the Russian Foundation for Basic Research (project no. 18-015-00042).
The LC-MS/MS analysis of proteins was performed in the Center for Collective Use “Human Proteome” (Institute of Biomedical Chemistry) supported by the Ministry of Science and Education of the Russian Federation the within the agreement no. 14.621.21.0017 (the unique identifier RFMEFI-62117X0017).
Supplementary materials are available in the electronic version of the paper at pbmc.ibmc.msk.ru.
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Сonflict of interests. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 2.Medvedev, A., Buneeva, O., and Glover, V., Biologics, 2007, vol. 1, no. 2, pp. 151–162.Google Scholar
- 6.Buneeva, O., Gnedenko, O., Zgoda, V., Kopylov, A., Glover, V., Ivanov, A., Medvedev, A., and Archakov, A., Proteomics, 2010, vol. 10, pp. 23–37.Google Scholar
- 7.Buneeva, O.A, Kopylov, A.T., Tikhonova, O.V., Zgoda, V.G., Medvedev, A.E., and Archakov, A.I., Biochemistry (Moscow), 2012, vol. 77, p. 1584–1599.Google Scholar
- 8.Szökö, É., Tábi, T., Riederer, P., Vécsei, L., and Magyar, K., J. Neural Transm. (Vienna), 2018 [Epub ahead of print] doi 10.1007/s00702-018-1853-9Google Scholar
- 10.Medvedev, A.E., Buneeva, O.A, Kopylov, A.T., Tikhonova, O.V., Medvedeva, M.V., Nerobkova, L.N., Kapitsa, I.G., and Zgoda, V.G., Biochemistry (Moscow), 2017, vol. 82, pp. 470–480.Google Scholar
- 14.Medvedev, A., Buneeva, O., Gnedenko, O., Fedchenko, V., Medvedeva, M., Ivanov, Y., Glover, V., and Sandler, M., J. Neural Transm., 2006, suppl. 71, pp. 97–103.Google Scholar
- 16.Buneeva, O.A., Gnedenko. O.V., Medvedeva, M.V., Ivanov, Yu.D., Glover, V., and Medvedev, A.E., Biomed. Khim., 2006, vol. 52, no. 4, pp. 413–418.Google Scholar
- 17.Buneeva, O.A., Kopylov, A.T., Zgoda, V.G., and Medvedev, A.E., Biomedical Chemistry: Research and Methods, 2018, vol. 1, no. 1, e00007. doi 10.18097/ bmcrm00007Google Scholar