Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid
Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid
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DOI：
10.1001/archneur.58.3.392
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发表时间：
2001-03-01
影响因子：
--
通讯作者：
Markesbery, WR
中科院分区：
文献类型：
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作者：
Lovell, MA;Markesbery, WR
背景：阿尔茨海默病 (AD) 患者的脑脊液 (CSF) 中氧化应激标记物增加，但由于 AD 患者和对照受试者之间的重叠，所报道的这些标记物均不是适当的诊断标记物。 目的：确定 AD 患者和年龄匹配对照受试者的脑室 CSF 中完整 DNA 中的 8-羟基鸟嘌呤 (8-OHG) 水平与游离 8-OHG 水平的比率。 DNA 氧化最显着的标记物是 8-OHG。方法：使用固相萃取柱从 18 名 AD 受试者和 7 名对照受试者尸检时采集的脑室 CSF 中分离出游离的 8-羟基 2'-脱氧鸟苷 (8-OHdG)。使用带有选择性离子监测的气相色谱/质谱法测量水解产物 8-OHG 的水平。从相同的 CSF 中分离出完整的 DNA，并测定完整结构中 8-OHG 的水平。使用稳定标记的 8-OHG 进行定量。结果：具有统计学意义（P
Background: Markers of oxidative stress are increased in cerebrospinal fluid (CSF) of patients with Alzheimer disease (AD), although none of those reported are appropriate diagnostic markers because of the overlap between patients with AD and control subjects.Objective: To determine the ratio of 8-hydroxyguanine (8-OHG) levels in intact DNA to free 8-OHG in the ventricular CSF of patients with AD and age-matched control subjects. The most prominent marker of DNA oxidation-is 8-OHG.Methods: Free 8-hydroxy 2'-deoxyguanosine (8-OHdG) was isolated from ventricular CSF taken at autopsy from 18 subjects with AD and 7 control subjects using solid-phase extraction columns. Levels were measured as the hydrolysis product, 8-OHG, using gas chromatography/mass spectrometry with selective ion monitoring. Intact DNA was isolated from the same CSF and the levels of 8-OHG were determined in the intact structures. Stable-labeled 8-OHG was used for quantification.Results: A statistically significant (P