Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production

被引：64

作者：

Cheignon, Clemence ^{[1
,2
,3
]}

Faller, Peter ^{[1
,2
]}

Testemale, Denis ^{[4
,5
]}

Hureau, Christelle ^{[1
,2
]}

Collin, Fabrice ^{[1
,2
,3
]}

机构：

[1] CNRS UPR 8241, LCC, 205 Route Narbonne, F-31062 Toulouse 09, France

[2] Univ Toulouse, UPS, INPT, F-31077 Toulouse, France

[3] Univ Toulouse, UMR Pharma Dev 152, IRD, Toulouse, France

[4] Univ Grenoble Alpes, Inst NEEL, F-38000 Grenoble, France

[5] CNRS, Inst NEEL, F-38000 Grenoble, France

来源：

METALLOMICS | 2016年 / 8卷 / 10期

基金：

欧洲研究理事会;

关键词：

AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; COPPER-BINDING; HYDROXYL RADICALS; MASS-SPECTROMETRY; PHYSIOLOGICAL PH; PEPTIDE; COORDINATION; COMPLEXES;

D O I：

10.1039/c6mt00150e

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the context of Alzheimer's disease (AD), the production of HO center dot by copper-amyloid beta (Ab) in the presence of ascorbate is known to be deleterious for the A beta peptide itself and also for the surrounding molecules, thus establishing a direct link between AD and oxidative stress. The metal-catalyzed oxidation (MCO) of A beta primarily targets the residues involved in copper coordination during HO center dot production. In the present work, we demonstrate that the oxidative damage undergone by A beta during MCO lead to a change in copper coordination, with enhanced catalytic properties that increases the rates of ascorbate consumption and HO center dot production, and the amount of HO center dot released by the system. This phenomenon is observed after the peptide has been sufficiently oxidized.

引用

页码：1081 / 1089

页数：9

共 47 条

[1] Zn impacts Cu coordination to amyloid-β, the Alzheimer's peptide, but not the ROS production and the associated cell toxicity [J].