S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease
S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease
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DOI：
10.1073/pnas.0705904104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Lipton, Stuart A.
中科院分区：
文献类型：
--
作者：
Fang, Jianguo;Nakamura, Tomohiro;Lipton, Stuart A.
过氧化物还原酶（Peroxiredoxins，Prx）是一个以硫氧还蛋白系统为电子供体还原细胞内过氧化物的过氧化物酶家族，在多种细胞区室中高度表达。在抗氧化剂Prx酶中，Prx 2在哺乳动物神经元中最丰富，使其成为防御氧化应激的主要候选者。在这里，我们报告说，Prx 2是S-亚硝基化（形成SNO-Prx 2）的反应与一氧化氮在两个关键的半胱氨酸残基（C51和C172），防止其与过氧化物反应。我们观察到增加SNO-Prx 2在人类帕金森氏病（PD）的大脑，和S-亚硝基化的Prx 2抑制其酶活性和保护功能的氧化应激。在PD中丢失的多巴胺能神经元变得特别脆弱。因此，我们的数据提供了亚硝化/氧化应激和神经退行性疾病如PD之间的直接联系。
Peroxiredoxins (Prx), a family of peroxidases that reduce intracellular peroxides with the thioredoxin system as the electron donor, are highly expressed in various cellular compartments. Among the antioxidant Prx enzymes, Prx2 is the most abundant in mammalian neurons, making it a prime candidate to defend against oxidative stress. Here we report that Prx2 is S-nitrosylated (forming SNO-Prx2) by reaction with nitric oxide at two critical cysteine residues (C51 and C172), preventing its reaction with peroxides. We observed increased SNO-Prx2 in human Parkinson's disease (PD) brains, and S-nitrosylation of Prx2 inhibited both its enzymatic activity and protective function from oxidative stress. Dopaminergic neurons, which are lost in PD, become particularly vulnerable. Thus, our data provide a direct link between nitrosative/oxidative stress and neurodegenerative disorders such as PD.