Influence of chelators and iron ions on the production and degradation of H2O2 by beta-amyloid-copper complexes.
beta-Amyloid peptide (Abeta) 1-42, involved in the pathogenesis of Alzheimer's disease, binds copper ions to form AbetaxCu(n) complexes that are able to generate H(2)O(2) in the presence of a reductant and O(2). The production of H(2)O(2) can be stopped with chelators. More reactive than H(2)O(2) itself, hydroxyl radicals HO() (generated when a reduced redox active metal complex interacts with H(2)O(2)) 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 H(2)O(2) associated to a pre-incubation step between ascorbate and AbetaxCu(n) allows to study the formation of H(2)O(2) but also, at the same time, its transformation by the copper complexes. AbetaxCu(n) peptides produce but do not efficiently degrade H(2)O(2). The reported analytic method, associated to precipitation experiments of copper-containing amyloid peptides, allows to study the inhibition of H(2)O(2) production by chelators. The action of a ligand such as EDTA is probably due to the removal of the copper ions from AbetaxCu(n), whereas bidentate ligands such as 8-hydroxyquinolines probably act via the formation of ternary complexes with AbetaxCu(n). The redox activity of these bidentate ligands can be modulated by the incorporation or the modification of substituents on the quinoline heterocycle.
Deraeve
Céline
C
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse cedex 4, France.
Pitie
Marguerite
M
Meunier
Bernard
B
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002412:Cations; D002614:Chelating Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006868:Hydrolysis; D007501:Iron / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D016229:Amyloid beta-Peptides; D002412:Cations; D002614:Chelating Agents; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron