Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells
Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells
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DOI：
10.1016/j.bbrc.2004.03.110
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发表时间：
2004-05-07
影响因子：
3.1
通讯作者：
Niki, E
中科院分区：
文献类型：
--
作者：
Kinumi, T;Kimata, J;Niki, E
DJ-1基因突变是常染色体隐性遗传性帕金森病的病因，但其生理功能尚不清楚。细胞经过氧化氢处理后，DJ-1等电点发生酸性移动。这表明DJ-1被修饰以响应氧化应激。在这里，我们报道了用蛋白质组学方法结合纳米喷雾界面液相色谱-电喷雾电离/线性离子陷阱质谱仪对DJ-1的酸性异构体进行结构表征。当人脐静脉内皮细胞暴露于过氧化氢时，DJ-1中的三种半胱氨酸都被氧化为半胱氨酸磺酸。虽然有一小部分Cys-46和Cys-53被氧化，但在礼来公司使用的过氧化氢浓度下，Cys-106被完全氧化。这些结果表明，在三个半胱氨酸残基中，Cys-106对氧化应激最敏感，而DJ-1的功能是通过Cys-106的氧化来调节细胞内的氧化还原状态的。(C)2004 Elsevier Inc.保留所有权利。
Mutation in DJ-1 gene is the cause of autosomal recessive Parkinson's disease, however, its physiological function remains unclear. The isoelectric point of DJ-1 shows an acidic shift after cells are treated with hydrogen peroxide. This suggests that DJ-1 is modified in response to oxidative stress. Here we report the structural characterization of an acidic isoform of DJ-1 using a proteomic approach with nanospray interface liquid chromotography-electrospray ionization/linear ion trap mass spectrometer. When human umbilical vein endothelial cells were exposed to hydrogen peroxide, all three cysteines in DJ-1 were oxidized to cysteine sulphonic acid. Although a small part of the Cys-46 and Cys-53 were oxidized, Cys-106 was oxidized completely at Lilly hydrogen peroxide concentration used here. These results suggest that Cys-106 is the most sensitive among three cysteine residues to oxidative stress, and that DJ-1 function is regulated in terms of the intracellular redox state, by oxidation of Cys-106. (C) 2004 Elsevier Inc. All rights reserved.