Buneeva O A, Kopylov A T, Nerobkova L N, Kapitsa I G, Zgoda V G, Medvedev A E
Institute of Biomedical Chemistry, Moscow, Russia.
Zakusov Institute of Pharmacology, Moscow, Russia.
Biomed Khim. 2017 Jul;63(4):316-320. doi: 10.18097/PBMC20176304316.
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 (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 MPTP-induced 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.
异吲哚酮（吲哚 - 2,3 - 二酮）是一种存在于哺乳动物大脑、外周器官和体液中的内源性吲哚。它作为一种神经保护剂，可降低帕金森病动物模型中运动障碍的表现。异吲哚酮的广泛生物活性与其与众多异吲哚酮结合蛋白的相互作用有关。本研究的目的是调查用1 - 甲基 - 4 - 苯基 - 1,2,3,6 - 四氢吡啶（MPTP）诱导的帕金森病小鼠（在给予这种神经毒素90分钟和7天后）大脑中异吲哚酮结合蛋白的概况。单次腹腔注射MPTP（30 mg/kg）后90分钟，旷场试验中出现运动障碍；MPTP给药7天后，小鼠的运动活性显著改善，但未达到对照水平。对异吲哚酮结合蛋白进行蛋白质组学分析的五项独立实验，最终可靠鉴定出96±12种蛋白质。MPTP诱导的运动障碍的发展伴随着异吲哚酮结合蛋白数量的显著减少（63±6；n = 5；p < 0.01）。MPTP给药7天后，鉴定出的蛋白质总数增加并达到对照水平（132±34；n = 4）。异吲哚酮结合蛋白的概况在每组小鼠中具有相当的特异性：在对照组中，这些蛋白（在两组MPTP处理的小鼠中均未发现）占总蛋白的70%以上。对于MPTP处理的小鼠，该参数分别为60%（MPTP给药后90分钟）和>82%（MPTP给药后7天）。在参与细胞骨架形成和胞吐作用、基因表达调控、细胞分裂和分化的异吲哚酮结合蛋白组以及参与信号转导的蛋白中发现了主要变化。
