Redox chemistry of copper-amyloid-β:: The generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state
Redox chemistry of copper-amyloid-β:: The generation of hydroxyl radical in the presence of ascorbate is linked to redox-potentials and aggregation state
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DOI：
10.1002/cbic.200700111
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发表时间：
2007-07-23
期刊：
影响因子：
3.2
通讯作者：
Faller, Peter
中科院分区：
文献类型：
--
作者：
Guilloreau, Luc;Combalbert, Sarah;Faller, Peter
β-淀粉样肽 (Aβ) 向淀粉样斑块的聚集是阿尔茨海默病的一个关键事件。根据淀粉样蛋白级联假说，Aβ 聚集体通过产生活性氧 (ROS) 对神经元有毒。铜离子发挥着重要作用，因为它们能够与 A beta 结合并影响其聚集特性。此外，Cu-A beta 应该直接参与 ROS 的产生。为了更好地了解这些反应，我们测量了 H2O 中心点的产生和 Cu-A beta 的氧化还原电位。将结果与其他生物铜肽复合物进行比较，以便深入了解生物相关性。 Cu-A beta 比铜与 Asp-Ala-His-Lys (Cu-DAHK) 的络合物产生更多的 H2O 中心点，但比与 Gly-His-Lys (Cu-GHK) 的络合物少。循环伏安法显示还原电位的顺序是Cu-GHK > Cu-Ap > Cu-DAHK，但氧化电位的顺序相反。因此，更容易的铜氧化还原循环与更高的 H2O 中心点产生相关。形式Aβ1-42的铜配合物显示出比形式Aβ1-40高五倍的HID中心点产生。时间依赖性和聚集研究表明，聚集中间体是导致 H2O 中心点产生增加的原因。
Aggregation of the beta-amyloid peptide (A beta) to amyloid plaques is a key event in Alzheimer's disease. According to the amyloid-cascade hypothesis, A beta aggregates are toxic to neurons through the production of reactive oxygen species (ROS). Copper ions play an important role, because they are able to bind to A beta and influence its aggregation properties. Moreover, Cu-A beta is supposed to be directly involved in ROS production. To get a better understanding of these reactions, we measured the production of HO center dot and the redox potential of Cu-A beta. The results were compared to other biological copper-peptide complexes in order to get an insight into the biological relevance. Cu-A beta produced more HO center dot than the complex of copper with Asp-Ala-His-Lys (Cu-DAHK), but less than with Gly-His-Lys (Cu-GHK). Cyclic voltommetry revealed that the order for reduction potential is Cu-GHK > Cu-Ap > Cu-DAHK, but for the oxidation potential the order is reversed. Thus, easier copper redox cycling correlated to higher HO center dot production. The copper complex of the form A beta 1-42 showed a HID center dot production five-times higher than that of the form A beta 1-40. Time-dependence and aggregation studies suggest that an aggregation intermediate is responsible for this increased HO center dot production.