کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1318175 | 1499482 | 2006 | 10 صفحه PDF | دانلود رایگان |
β-Amyloid peptide (Aβ) 1–42, involved in the pathogenesis of Alzheimer’s disease, binds copper ions to form Aβ · Cun complexes that are able to generate H2O2 in the presence of a reductant and O2. 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 Aβ · Cun allows to study the formation of H2O2 but also, at the same time, its transformation by the copper complexes. Aβ · Cun 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 Aβ · Cun, whereas bidentate ligands such as 8-hydroxyquinolines probably act via the formation of ternary complexes with Aβ · Cun. The redox activity of these bidentate ligands can be modulated by the incorporation or the modification of substituents on the quinoline heterocycle.
Journal: Journal of Inorganic Biochemistry - Volume 100, Issue 12, December 2006, Pages 2117–2126