Increased oxidative damage to DNA in ALS patients
Increased oxidative damage to DNA in ALS patients
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DOI：
10.1016/s0891-5849(00)00349-x
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发表时间：
2000-10-01
影响因子：
7.4
通讯作者：
Cudkowicz, M
中科院分区：
文献类型：
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作者：
Bogdanov, M;Brown, RH;Cudkowicz, M
虽然肌萎缩侧索硬化症(ALS)的病因尚不清楚，但大量证据表明，氧化毒性与该病的神经元死亡有关。我们在单个时间点检测了ALS、其他神经系统疾病或无已知疾病的受试者血浆、尿液和脑脊液(CSF)中DNA氧化损伤标志物8-羟基-2‘-脱氧鸟苷(8OH2’DG)的水平。我们还测量了ALS患者和对照组9个月内血浆和尿液中8OH2‘DG水平的变化率，并探讨了其与疾病严重程度的关系。ALS组每种液体中8OH2‘DG水平均显著高于对照组。在所有受试者中，血浆和脑脊液8OH2‘DG水平随着年龄的增长而增加，为氧化损伤在正常衰老中的作用提供了进一步的证据。血浆和尿中sOH2‘DG水平仅在ALS组随时间延长而显著升高。尿8OH2‘DG水平随时间增加的速率与病情严重程度显著相关。这些发现与氧化病理伴随着ALS的神经退变过程的假设是一致的，并表明8OH2‘DG可能为监测这种疾病的治疗干预提供了一个有用的工具。(C)2000年爱思唯尔科学公司。
Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, substantial evidence indicates that oxidative toxicity is associated with neuronal death in this disease. We examined levels of a well-established marker of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OH2'dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measured the rate of change of 8OH2'dG levels in plasma and urine from ALS and in urine from control subjects over 9 months and examined the relationship to disease severity. In each fluid, 8OH2'dG levels were significantly elevated in the ALS group as compared to control subjects. In all subjects, the plasma and CSF 8OH2'dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine sOH2'dG levels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2'dG levels with time was significantly correlated with disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and suggest that 8OH2'dG may provide a useful tool for monitoring therapeutic interventions in this disease. (C) 2000 Elsevier Science Inc.