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Membrane Binding Strongly Affecting the Dopamine Reactivity Induced by Copper Prion and Copper/Amyloid-β (Aβ) Peptides. A Ternary Copper/Aβ/Prion Peptide Complex Stabilized and Solubilized in Sodium Dodecyl Sulfate Micelles.
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2019-12-23 , DOI: 10.1021/acs.inorgchem.9b03153
Chiara Bacchella 1 , Stefania Nicolis 1 , Simone Dell'Acqua 1 , Enrico Rizzarelli 2 , Enrico Monzani 1 , Luigi Casella 1
Affiliation  

The combination between dyshomeostatic levels of catecholamine neurotransmitters and redox-active metals such as copper and iron exacerbates the oxidative stress condition that typically affects neurodegenerative diseases. We report a comparative study of the oxidative reactivity of copper complexes with amyloid-β (Aβ40) and the prion peptide fragment 76-114 (PrP76-114), containing the high-affinity binding site, toward dopamine and 4-methylcatechol, in aqueous buffer and in sodium dodecyl sulfate micelles, as a model membrane environment. The competitive oxidative and covalent modifications undergone by the peptides were also evaluated. The high binding affinity of Cu/peptide to micelles and lipid membranes leads to a strong reduction (Aβ40) and quenching (PrP76-114) of the oxidative efficiency of the binary complexes and to a stabilization and redox silencing of the ternary complex CuII/Aβ40/PrP76-114, which is highly reactive in solution. The results improve our understanding of the pathological and protective effects associated with these complexes, depending on the physiological environment.

中文翻译:

膜结合强烈影响铜Pri蛋白和铜/淀粉样β(Aβ)肽诱导的多巴胺反应性。在十二烷基硫酸钠胶束中稳定并溶解的三元铜/Aβ/ Prion肽复合物。

儿茶酚胺神经递质的体内稳态水平与铜和铁等氧化还原活性金属之间的结合加剧了通常影响神经退行性疾病的氧化应激状况。我们报告了铜与淀粉样蛋白-β(Aβ40)和the病毒肽片段76-114(PrP76-114)的氧化反应性的比较研究,其中含有高亲和力结合位点,对多巴胺和4-甲基邻苯二酚在水中缓冲液和十二烷基硫酸钠胶束,作为模型膜环境。还评估了肽所经历的竞争性氧化和共价修饰。Cu /肽对胶束和脂质膜的高结合亲和力导致二元复合物的氧化效率大大降低(Aβ40)和猝灭(PrP76-114),并使三元复合物CuII /Aβ40稳定和氧化还原沉默/ PrP76-114,在溶液中具有高反应性。结果根据生理环境改善了我们对与这些复合物相关的病理和保护作用的理解。
更新日期:2019-12-25
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