PROCESSING OF OXIDATIVE STRESS IN ALZHEIMER'S DISEASE

阿尔茨海默病中氧化应激的处理

• 批准号: 6160490
• 负责人: V A BOHR
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160490
• 关键词: Alzheimer's disease; DNA damage; DNA repair; family genetics; fibroblasts; fluorescence; gas chromatography mass spectrometry; oxidative stress; plasmids; radiation genetics; tissue /cell culture

Summary of work: Recently, it was demonstrated (Prashad et al.) that cells from patients with familial Alzheimer disease (AD) had an altered response to fluorescent light (FL) exposure as compared to cells from unaffected individuals, suggesting that there may be some deficiency in the DNA repair processing of oxidative lesions induced by FL in AD. This project was initiated to develop a better understanding of the DNA repair capacity of AD for FL induced lesions. The formation and repair of oxidative base lesions in AD and normal fibroblasts was measured after exposure to FL using gas chromatography/mass spectrometry (GC/MS) analysis. Several oxidative DNA lesions were induced in AD and normal cells by exposure to FL. The oxidative lesions induced by FL exposure include 5-hydroxycytosine, formamidopyrimidine, and 8-hydroxy guanine. Additionally, the capacity of AD cells to repair oxidative DNA damage is being investigated using an in vitro DNA repair synthesis assay. In vitro DNA repair synthesis was carried out by whole cell extracts from AD and normal cells on plasmid DNA damaged by gamma-irradiation. This substrate was repaired efficiently by whole cell extracts from both AD and normal cells. Similar in vitro assays using plasmid DNA damaged by various oxidative sources are currently in progress.

工作总结：最近，它得到了演示(Prashad等人)那 家族性阿尔茨海默病(AD)患者的细胞发生改变 对荧光光(FL)暴露的反应与来自 未受影响的个体，表明可能存在某些缺陷 FL诱导的AD氧化损伤的DNA修复过程。这 该项目的发起是为了更好地了解DNA修复 AD对FL所致损伤的保护作用。浅谈汽车车辙的形成与修复 检测AD和正常成纤维细胞的氧化碱基损伤 用气相色谱/质谱仪(GC/MS)研究FL暴露 分析。阿尔茨海默病患者和正常对照组的DNA氧化损伤 细胞经FL处理后，细胞数增加。FL暴露所致的氧化损伤 包括5-羟基胞嘧啶、甲酰胺基嘧啶和8-羟基鸟嘌呤。 此外，AD细胞修复氧化DNA损伤的能力是 正在使用体外DNA修复合成试验进行研究。离体 用AD和AD的全细胞提取液进行DNA修复合成 质粒DNA上的正常细胞受到伽马射线的损伤。这种衬底 AD和正常人的全细胞提取液有效地修复了 细胞。用不同种类的DNA损伤的质粒DNA进行相似的体外检测 氧化源目前正在进行中。