The Effect of Neurotoxin MPTP Administration to Mice on the Proteomic Profile of Brain Isatin-Binding Proteins

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 characterized by maximal manifestation of locomotor impairments (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 MPTPinduced 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.