Influence of chelators and iron ions on the production and degradation of H2O2 by β-amyloid-copper complexes
Influence of chelators and iron ions on the production and degradation of H2O2 by β-amyloid-copper complexes
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DOI：
10.1016/j.jinorgbio.2006.08.005
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发表时间：
2006-12-01
影响因子：
3.9
通讯作者：
Meunier, Bernard
中科院分区：
文献类型：
--
作者：
Deraeve, Celine;Pitie, Marguerite;Meunier, Bernard
β-淀粉样蛋白肽（Aβ）1-42涉及阿尔茨海默氏病的发病机理，结合铜离子，形成β（。）Cu-n络合物，能够在还原剂和O-2的情况下能够产生H2O2。 H2O2的生产可以用螯合剂停止。比H2O2本身更具反应性，羟基自由基HO。 （当减少的氧化还原活性金属复合物与H2O2相互作用时，产生）也可能参与疾病期间造成脑损伤的氧化应激。我们在本工作中报告了一种监测螯合剂对金属 - 淀粉样蛋白肽过氧化氢产生的影响的方法。与抗坏血酸和β（。）Cu-N之间的预孵育步骤相关的H2O2添加允许研究H2O2的形成，同时也可以研究其铜络合物的转化。 β（。）Cu-N肽会产生，但不会有效降解H2O2。报道的分析方法与含铜淀粉样蛋白肽的降水实验相关，可以研究螯合剂对H2O2产生的抑制作用。诸如EDTA之类的配体的作用可能是由于从β（。）Cu-n中去除铜离子，而双齿配体（例如8-羟基喹啉）可能通过用β（。）cu-n形成三元复合物。这些二齿配体的氧化还原活性可以通过掺入或修饰喹啉杂环上的取代基来调节。 （c）2006 Elsevier Inc.保留所有权利。
beta-Amyloid peptide (A beta) 1-42, involved in the pathogenesis of Alzheimer's disease, binds copper ions to form A beta (.) Cu-n complexes that are able to generate H2O2 in the presence of a reductant and O-2. The production of H2O2 can be stopped with chelators. More reactive than H2O2 itself, hydroxyl radicals HO. (generated when a reduced redox active metal complex interacts with H2O2) are also probably involved in the oxidative stress that creates brain damage during the disease. We report in the present work a method to monitor the effect of chelating agents on the production of hydrogen peroxide by metallo-amyloid peptides. The addition of H2O2 associated to a pre-incubation step between ascorbate and A beta (.) Cu-n allows to study the formation of H2O2 but also, at the same time, its transformation by the copper complexes. A beta (.) Cu-n peptides produce but do not efficiently degrade H2O2. The reported analytic method, associated to precipitation experiments of copper-containing amyloid peptides, allows to study the inhibition of H2O2 production by chelators. The action of a ligand such as EDTA is probably due to the removal of the copper ions from A beta (.) Cu-n, whereas bidentate ligands such as 8-hydroxyquinolines probably act via the formation of ternary complexes with A beta (.) Cu-n. The redox activity of these bidentate ligands can be modulated by the incorporation or the modification of substituents on the quinoline heterocycle. (c) 2006 Elsevier Inc. All rights reserved.