阿尔茨海默病患者外周血淋巴细胞 8-氧鸟嘌呤 DNA 糖苷酶 1（OGG1）的表达及 p53、TNF-α 蛋白水平的变化。
Expression of 8-oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF-αlpha proteins in peripheral lymphocytes of patients with Alzheimer's disease.
机构信息
Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poland.
出版信息
Folia Neuropathol. 2011;49(2):123-31.
The aim of the study was to determine the extent of oxidative DNA damage (levels of 8-oxo2dG) and expression of OGG1 and p53 and TNF-α proteins in lymphocytes of Alzheimer's disease (AD) patients and a control group. The studies were conducted on 41 patients with AD, including 25 women and 16 men aged 34-84 years. The control group included 51 individuals, 20 women and 31 men aged 22-83 years. The level of 8-oxo2dG was determined using HPLC/EC/UV, and the level of OGG1 and p53 and TNF-α proteins was determined with the Western blot method. The results showed that both proteins participating in DNA repair (OGG1, p53) and the inflammatory protein TNF-α are involved in pathogenesis of neurodegenerative diseases. It also seems that a specific system for DNA repair (OGG1) may contribute to downregulation of the inflammatory factor (TNF-α) level, especially in the early stages of dementia. Moreover, the results showed that p53 protein can fulfil its function in DNA damage repair only in early stages of dementia. It is possible that OGG1 and p53 and TNF-α proteins together or separately may be involved in pathogenesis of AD by repair of oxidative DNA damage and/or apoptosis.
本研究旨在确定阿尔茨海默病（AD）患者和对照组淋巴细胞中氧化 DNA 损伤（8-oxo2dG 水平）、OGG1 和 p53 及 TNF-α 蛋白的表达程度。研究共纳入 41 例 AD 患者，其中女性 25 例，男性 16 例，年龄 34-84 岁；对照组纳入 51 例个体，其中女性 20 例，男性 31 例，年龄 22-83 岁。采用 HPLC/EC/UV 法测定 8-oxo2dG 水平，采用 Western blot 法测定 OGG1、p53 和 TNF-α 蛋白水平。结果表明，参与 DNA 修复（OGG1、p53）和炎症蛋白 TNF-α 的两种蛋白均参与神经退行性疾病的发病机制。似乎特定的 DNA 修复系统（OGG1）可能有助于下调炎症因子（TNF-α）水平，尤其是在痴呆的早期阶段。此外，结果表明，p53 蛋白仅在痴呆的早期阶段才能发挥其在 DNA 损伤修复中的作用。OGG1、p53 和 TNF-α 蛋白可能通过修复氧化 DNA 损伤和/或细胞凋亡共同或单独参与 AD 的发病机制。
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