Identification of oxidized plasma proteins in Alzheimer's disease
Identification of oxidized plasma proteins in Alzheimer's disease
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DOI：
10.1016/s0006-291x(02)00420-5
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发表时间：
2002-05-24
影响因子：
3.1
通讯作者：
Gracy, RW
中科院分区：
文献类型：
--
作者：
Choi, JG;Malakowsky, CA;Gracy, RW
活性氧对蛋白质的修饰在阿尔茨海默病(AD)的发病机制中占有重要地位。以前，我们曾在AD患者的血浆中观察到特定的氧化蛋白[生物化学。生物群落。[中英文摘要]Re.Commun.275(2000)678]。对AD患者和年龄匹配的对照组的血浆进行双向凝胶电泳(2-DE)。通过与2，4-二硝基苯肼反应，再用抗DNP抗体进行Western blotting，检测到含有新羰基的氧化蛋白质。观察到7个主要的氧化蛋白斑点(等电点为4.7-5.5；分子质量为45-65 kDa)，在AD和非AD患者的血浆样本中都有不同程度的氧化。基质辅助激光解吸质谱仪(MALDI-TOF/MS)表明，这些氧化蛋白是纤维蛋白原-伽马链前体蛋白和α-1-抗胰蛋白酶前体的异构体。与对照组相比，AD受试者血浆中这些蛋白质的特定氧化指数高出2到6倍。这两种蛋白质此前都被认为与该病的病理有关。这些蛋白的氧化异构体有可能作为AD的生物标志物。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
The modification of proteins by reactive oxygen species is central to the pathology of Alzheimer's disease (AD). Previously, we have observed specific oxidized proteins in blood plasma of AD subjects [Biochem. Biophys. Res. Commun. 275 (2000) 678]. Plasma from AD subjects and age-matched controls was subjected to two-dimensional gel electrophoresis (2-DE). Oxidized proteins with new carbonyl groups were detected by reaction with 2,4-dinitrophenythydrazine, followed by Western blotting with anti-DNP antibody. Seven principal oxidized protein spots (isoelectric point = 4.7-5.5; molecular mass = 45-65 kDa) were observed, with varying levels of oxidation in plasma samples from both AD and non-AD subjects. Matrix-assisted laser desorption mass spectroscopy (MALDI-TOF/MS) revealed that these oxidized proteins were isoforms of fibrinogen gamma-chain precursor protein and of alpha-1-antitrypsin precursor. These proteins exhibited a two- to sixfold greater specific oxidation index in plasma from AD subjects when compared to controls. Both these proteins have been previously implicated in the pathology of the disease. It is possible that oxidized isoforms of these proteins may serve as biomarkers for AD. (C) 2002 Elsevier Science (USA). All rights reserved.