Buneeva O A, Kopylov A T, Zgoda V G, Medvedev A E
Institute of Biomedical Chemistry, Moscow, Russia.
Biomed Khim. 2018 Aug;64(4):354-359. doi: 10.18097/PBMC20186404354.
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. 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 substances. Taking into account 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.
异吲哚酮（吲哚 - 2,3 - 二酮）是一种内源性吲哚，存在于人类和动物的大脑、外周组织及生物体液中。其广泛的生物活性是通过与众多异吲哚酮结合蛋白相互作用来实现的；这些蛋白包括在神经退行性病变发展过程中起重要作用的蛋白质。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的作用相当。在本研究中，研究了连续21天给予司来吉兰（1毫克/千克）和异吲哚酮（20毫克/千克）对小鼠肝脏异吲哚酮结合蛋白谱的影响。以5 - 氨基己酰异吲哚酮作为亲和配体，对对照小鼠肝脏异吲哚酮结合蛋白进行蛋白质组学分析，鉴定出105种蛋白质。用低剂量异吲哚酮处理动物会使异吲哚酮结合蛋白总数略有减少（降至91种），而注射司来吉兰则会使其略有增加（增至120种）。三组共有75种蛋白质；它们分别占已鉴定肝脏异吲哚酮结合蛋白总数的62.5%（司来吉兰处理的小鼠）、71%（对照小鼠）和82%（异吲哚酮处理的小鼠）。对用异吲哚酮（20毫克/千克）或司来吉兰（1毫克/千克）处理21天的小鼠的异吲哚酮结合蛋白进行蛋白质组学分析，发现了一组对这些物质给药敏感的代表性蛋白质（n = 30）。考虑到先前获得的结果，合理的推测是异吲哚酮结合蛋白谱的变化可能归因于异吲哚酮和司来吉兰在肝脏中的积累，以及它们与靶蛋白的相互作用阻止了靶蛋白随后与亲和吸附剂的结合。在这种情况下，在用司来吉兰或异吲哚酮处理动物后，对照动物中未与亲和吸附剂（固定化异吲哚酮类似物）结合的已鉴定肝脏异吲哚酮结合蛋白似乎是在体内与异吲哚酮直接相互作用的特异性靶标。
