Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis

Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis
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DOI:
10.1002/ana.410420416
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发表时间:
1997-10-01
影响因子:
11.2
通讯作者:
Brown, RH
Brown, RH
中科院分区:
医学1区
文献类型:
--
作者:
Beal, MF;Ferrante, RJ;Brown, RH

文献摘要

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在散发性和家族性肌萎缩侧索硬化症(ALS)相关的超氧化物歧化酶突变中,神经元变性的发病机制可能与氧化应激有关。过氧亚硝酸盐是氧化应激的主要介体,它是由超氧化物和一氧化氮反应形成的。3-硝基酪氨酸是过氧亚硝酸盐介导的氧化损伤的一种相对特异的标志物,在本研究中,生化测量显示ALS患者腰椎和胸髓中3-硝基-4-羟基苯乙酸浓度升高。散发性和家族性ALS患者运动神经元3-硝基酪氨酸免疫反应增强。神经控制的脑缺血患者也表现出3-硝基酪氨酸免疫反应增强,这些发现表明过氧亚硝酸盐介导的氧化损伤可能在散发性和家族性ALS的发病机制中发挥作用。
The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite, In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity, These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.