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

Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production.
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DOI:
10.1039/c6mt00150e
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发表时间:
2016-10-01
期刊:
Metallomics : integrated biometal science
影响因子:
--
通讯作者:
Collin F
Collin F
中科院分区:
其他
文献类型:
--
作者:
Cheignon C;Faller P;Testemale D;Hureau C;Collin F

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在阿尔茨海默病 (AD) 的背景下,已知抗坏血酸存在下铜淀粉样蛋白 β (Aβ) 会产生 H2O•,这对 Aβ 肽本身以及周围的分子有害,从而在 AD 和氧化应激之间建立了直接联系。 Aβ 的金属催化氧化 (MCO) 主要针对 H2O• 生产过程中参与铜配位的残基。在目前的工作中,我们证明了 MCO 期间 Aβ 遭受的氧化损伤导致铜配位发生变化,催化性能增强,从而增加了抗坏血酸消耗和 H2O• 生成速率以及系统释放的 H2O• 量。这种现象是在肽被充分氧化后观察到的。
In the context of Alzheimer’s disease (AD), the production of HO• by copper–amyloid beta (Aβ) in the presence of ascorbate is known to be deleterious for the Aβ peptide itself and also for the surrounding molecules, thus establishing a direct link between AD and oxidative stress. The metal-catalyzed oxidation (MCO) of Aβ primarily targets the residues involved in copper coordination during HO• production. In the present work, we demonstrate that the oxidative damage undergone by Aβ during MCO lead to a change in copper coordination, with enhanced catalytic properties that increases the rates of ascorbate consumption and HO• production, and the amount of HO• released by the system. This phenomenon is observed after the peptide has been sufficiently oxidized.
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