The effect of neuroprotector isatin on binding of some model proteins with beta-amyloid peptide: a biosensor study

Abstract

The amyloid-beta peptide 1-42 formed during proteolytic processing of the amyloid precursor protein (APP) plays a key role in the development or progression of Alzheimer's disease (AD) and other pathologies associated with formation of protein aggregates in the central nervous system. Recent proteomic profiling of mouse and rat brain preparations by means of beta-amyloid peptide immobilized on Affigel-10 revealed a large group of amyloid-binding proteins (n>80). Many (about 25%) of these proteins were previously identified as isatin-binding proteins. The aim of this study was to validate direct interaction between beta-amyloid peptide and highly purified intact and oxidized peroxiredoxin, M-type pyruvate kinase, alpha-enolase, and the effect of isatin on this interaction. The study performed using SPR-based Biacore 3000 and Biacore X100 biosensors has shown that all the proteins form molecular complexes with immobilized beta-amyloid peptide. The Kd values for these complexes varied from 8.36х10-8 M (peroxiredoxin) to 1.97х10-6 M (alpha-enolase). Oxidative modification of investigated proteins caused opposite effects on complexes of these peptides with beta-amyloid. The endogenous neuroprotector isatin increased dissociation of complexes formed by beta-amyloid peptide with both intact proteins (peroxiredoxin, glyceraldehyde-3-phosphate dehydrogenase) and/or oxidized proteins (peroxiredoxin, pyruvate kinase) used in this study.

Isatin‐induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction

“…This strengthens a recently proposed role of isatin as a regulator of PPIs in living organisms. Taken together with previous data on decreased affinity of some PPIs in the presence of isatin these results indicate that isatin can exhibit multidirectional effects on PPIs: an increase in affinity of one type of PPIs and a decrease in affinity of other type of PPIs. At the same time, insensitivity of some pairs of PPIs investigated in this study to isatin also indicates that the regulatory effects of isatin on PPI are rather specific and do not cover all possible PPIs.…”

“…We have hypothesized that in addition to direct action on particular protein targets, isatin can act as a regulator of protein–protein interactions (PPIs). Indeed, results of our recent studies suggest that isatin can decrease affinity of some PPI . In this study we performed an surface plasmon resonance (SPR)‐based biosensor analysis for PPIs, which would demonstrate altered affinity in the presence of isatin.…”

Comparative proteomic analysis of mouse liver and brain isatin-binding proteins

“…Для подавляющего большинства идентифицированных изатин-связывающих белков (особенно ферментов) функциональное значение взаимодействия с изатином остается неясным. С учётом появляющихся данных о влиянии изатина на различные белок-белковые взаимодействия [16][17][18], различия в профиле изатин-связывающих белков мозга и печени могут свидетельствовать об участии идентифицированных белков в различных (суб)интерактомах. Нельзя исключить также, что обнаруженные различия в профиле изатин-связывающих белков, по-видимому, играют важную роль в специфических эффектах изатина в определённых органах.…”

The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins

“…Для подавляющего большинства идентифицированных изатин-связывающих белков (особенно ферментов) функциональное значение взаимодействия с изатином остается неясным. С учётом данных о влиянии изатина на различные белок-белковые взаимодействия [21][22][23] есть все основания полагать, что изменение профиля изатин-связывающих белков в динамике МФТП-индуцированного паркинсонизма отражает изменения интерактома, вызванные как введением нейротоксина, так и последующими (по-видимому, компенсаторными?) процессами в клетках.…”