Buneeva O A, Kapitsa I G, Ivanova E A, Kopylov A T, Zgoda V G, Medvedev A E
Institute of Biomedical Chemistry, Moscow, Russia.
Zakusov Institute of Pharmacology, Moscow, Russia.
Biomed Khim. 2019 Aug;65(5):407-417. doi: 10.18097/PBMC20196505407.
Isatin (indol-2,3-dione), an endogenous biofactor found in the brain, peripheral tissues and biological body fluids of humans and animals, exhibits a wide range of biological and pharmacological activities. They are realized via interaction with numerous isatin-binding proteins. Some of these proteins identified during proteomic profiling of the brain 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 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. Thus identified brain isatin-binding proteins of the control animals obviously represent specific targets that interact directly with isatin (and also with deprenyl) . Isatin or deprenyl administered to animals interact with these proteins and thus inhibit their binding to the affinity sorbent (immobilized isatin analogue).
异吲哚酮（吲哚 - 2,3 - 二酮）是一种在人类和动物的大脑、外周组织及生物体液中发现的内源性生物因子，具有广泛的生物学和药理活性。这些活性是通过与众多异吲哚酮结合蛋白相互作用来实现的。在对大脑进行蛋白质组分析时鉴定出的其中一些蛋白质与神经退行性病变的发展有关。在神经保护作用方面，异吲哚酮的作用与用于治疗帕金森病的药物司来吉兰（丙炔苯丙胺）的作用相当。在本研究中，我们研究了给小鼠单次注射异吲哚酮（100 mg/kg）和丙炔苯丙胺（10 mg/kg）对大脑异吲哚酮结合蛋白谱的影响。对用异吲哚酮或丙炔苯丙胺处理的小鼠大脑异吲哚酮结合蛋白进行比较蛋白质组分析，结果鉴定出一组对这些物质给药敏感的代表性蛋白质（n = 200）。异吲哚酮结合蛋白谱的变化可能明显归因于异吲哚酮和丙炔苯丙胺在大脑中的积累及其与靶蛋白的相互作用；这会阻止蛋白质与亲和吸附剂结合。因此，对照动物中鉴定出的大脑异吲哚酮结合蛋白显然代表了直接与异吲哚酮（以及丙炔苯丙胺）相互作用的特定靶点。给动物注射的异吲哚酮或丙炔苯丙胺与这些蛋白质相互作用，从而抑制它们与亲和吸附剂（固定化异吲哚酮类似物）的结合。
