过氧化物还原蛋白
化学
肽
生物化学
淀粉样前体蛋白
P3肽
β淀粉样蛋白
淀粉样蛋白(真菌学)
阿尔茨海默病
酶
医学
病理
过氧化物酶
无机化学
疾病
作者
O. A. Buneeva,O. V. Gnedenko,М. В. Медведева,А. С. Иванов,А. Е. Медведев
出处
期刊:Biomeditsinskaia khimiia
日期:2016-01-01
卷期号:62 (6): 720-724
被引量:8
标识
DOI:10.18097/pbmc20166206720
摘要
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.Beta-amiloidnyĭ peptid (1-42), obrazuiushchiĭsia v rezul'tate proteoliticheskogo protsessinga transmembrannogo belka-predshestvennika amiloida, rassmatrivaetsia v kachestve "kliuchevogo igroka" v razvitii bolezni Al'tsgeĭmera (AD) i drugikh patologicheskikh sostoianiĭ, obuslovlennykh obrazovaniem i nakopleniem belkovykh agregatov v tsentral'noĭ nervnoĭ sisteme. V khode proteomnogo profilirovaniia preparatov mozga intaktnykh krys i mysheĭ, provedennogo ranee s ispol'zovaniem v kachestve affinnogo sorbenta affigelia-10 s immobilizovannym beta-amiloidnym peptidom, bylo identifitsirovano bolee 80 individual'nykh belkov, spetsificheski sviazyvaiushchikhsia s étim ligandom. Mnogie iz nikh byli obnaruzheny ranee kak belki, sviazyvaiushchiesia s éndogennym neĭroprotektorom izatinom. Tsel'iu dannogo issledovaniia byla priamaia éksperimental'naia proverka vzaimodeĭstviia vysokoochishchennykh intaktnykh i okislennykh preparatov peroksiredoksina, piruvatkinazy myshechnogo tipa i al'fa-enolazy s immobilizovannym beta-amiloidnym peptidom i vliianie izatina na étot protsess. Po dannym biosensornogo analiza s ispol'zovaniem opticheskikh SPR-biosensorov Biacore 3000 i Biacore X100 vse issledovannye belki obrazovyvali molekuliarnye kompleksy s immobilizovannym beta-amiloidnym peptidom. Znacheniia Kd étikh kompleksov var'irovali ot 8,36kh10-8 M (u peroksiredoksina) do 1,97kh10-6 M (u al'fa-enolazy). Okislitel'naia modifikatsiia issledovannykh belkov okazyvala raznonapravlennoe vliianie na prochnost' kompleksov s beta-amiloidnym peptidom, a éndogennyĭ neĭroprotektor izatin povyshal dissotsiatsiiu kompleksov beta-amiloidnogo peptida s riadom intaktnykh (peroksiredoksin, GAFD) i/ili podvergnutykh okislitel'noĭ modifikatsii (peroksiredoksin, piruvatkinaza) model'nykh belkov.
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