Protein oxidation in the brain in Alzheimer's disease
Protein oxidation in the brain in Alzheimer's disease
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DOI：
10.1016/s0306-4522(00)00580-7
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Markesbery, WR
中科院分区：
文献类型：
--
作者：
Aksenov, MY;Aksenova, MV;Markesbery, WR
在这项研究中，我们使用免疫组织化学和二维指纹的氧化修饰蛋白（二维Oxyblot）一起研究蛋白质羰基形成在阿尔茨海默病的大脑。在6名阿尔茨海默病患者和6名年龄匹配的对照受试者的海马和海马旁回、上级和颞中回切片中检测到蛋白质氧化增加，但在小脑中未检测到。在两个大脑区域严重影响阿尔茨海默氏病的病理，突出的蛋白质羰基免疫反应性定位在细胞质中的神经元没有视觉病理形态学变化和退化的神经元，这表明细胞内的蛋白质可能会受到显着影响的氧化修饰。二维电泳后，使用特异性抗体鉴定了一些单个蛋白质的位置，并对蛋白质羰基进行了免疫印迹分析。这些研究证明了在阿尔茨海默病和对照脑提取物中β-微管蛋白、β-肌动蛋白和肌酸激酶BB中存在蛋白质羰基免疫反应性。在与胶质细胞酸性蛋白和tau亚型相匹配的斑点中检测不到蛋白质羰基。β-肌动蛋白和肌酸激酶BE中的特定蛋白质羰基水平在阿尔茨海默病中显著高于对照脑提取物。β-微管蛋白没有表现出显着增加特定的蛋白质羰基含量在阿尔茨海默氏病brain.We认为，氧化应激诱导的损伤可能涉及不同的细胞内蛋白质，包括关键酶和结构蛋白的选择性修饰，这之前，并可能导致神经元的神经退行性变在阿尔茨海默氏病brain. We建议。(C)2001年IBRO。由Elsevier Science Ltd.出版，版权所有。
In this study we used immunohistochemistry and two-dimensional fingerprinting of oxidatively modified proteins (two-dimensional Oxyblot) together to investigate protein carbonyl formation in the Alzheimer's disease brain. Increased protein oxidation was detected in sections from the hippocampus and parahippocampal gyrus, superior and middle temporal gyri of six Alzheimer's disease and six age-matched control human subjects, but not in the cerebellum. In two brain regions severely affected by Alzheimer's disease pathology, prominent protein carbonyl immunoreactivity was localized in the cytoplasm of neurons without visual pathomorphological changes and degenerating neurons, suggesting that intracellular proteins might be significantly affected by oxidative modifications. Following two-dimensional electrophoresis the positions of some individual proteins were identified using specific antibodies, and immunoblot analysis for protein carbonyls was performed. These studies demonstrated the presence of protein carbonyl immunoreactivity in beta -tubulin, beta -actin and creatine kinase BB in Alzheimer's disease and control brain extracts. Protein carbonyls were undetectable in spots matching glial fibrillary acidic protein and tau isoforms. Specific protein carbonyl levels in beta -actin and creatine kinase BE were significantly higher in Alzheimer's disease than in control brain extract. beta -Tubulin did not demonstrate a significant increase in specific protein carbonyl content in Alzheimer's disease brains.We suggest that oxidative stress-induced injury may involve the selective modification of different intracellular proteins, including key enzymes and structural proteins, which precedes and may lead to the neurofibrillary degeneration of neurons in the Alzheimer's disease brain. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.