Methionine regulates copper/hydrogen peroxide oxidation products of Abeta

Metal-catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid beta peptide (Abeta), the major biomarker of AD, in the presence of copper ions reduces Cu(2+) to Cu(+) and catalyses the formation of H(2)O(2) that subsequently induces radicals t...

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Bibliographic Details
Published in:Journal of peptide science 2005-06, Vol.11 (6), p.353-360
Main Authors: Ali, Feda E, Separovic, Frances, Barrow, Colin J, Cherny, Robert A, Fraser, Fiona, Bush, Ashley I, Masters, Colin L, Barnham, Kevin J
Format: Article
Language:English
Subjects:
Alzheimer Disease
Amino Acids - chemistry
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - metabolism
Catalysis
Copper - pharmacology
Horseradish Peroxidase
Humans
Hydrogen Peroxide - pharmacology
Methionine - pharmacology
Oxidation-Reduction
Peptide Fragments - chemistry
Spectrometry, Fluorescence
Spectrometry, Mass, Electrospray Ionization
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Summary:Metal-catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid beta peptide (Abeta), the major biomarker of AD, in the presence of copper ions reduces Cu(2+) to Cu(+) and catalyses the formation of H(2)O(2) that subsequently induces radicals through Fenton chemistry. Abeta is also subject to attack by free radicals, where the presence of Cu(2+) in conjunction with H(2)O(2) catalyses oxygenation, primarily at the methionine sulfur atom. This work investigates MCO of Abeta, to gain further insight into the role of oxidative stress in AD. By combining a fluorescence assay with gel electrophoresis to monitor MCO reactions of Abeta (1-28) in the presence and absence of methionine it was determined that methionine can both protect some residues against MCO and promote the oxidation of Tyr(10) specifically. Electrospray ionization mass spectrometric analysis of methionine MCO products indicated the formation of methionine sulfoxide, methionine sulfone and related hydroxylated products. Similar products could be formed from the oxidation of Met(35) of Abeta and may relate to changes in properties of the peptide following MCO.
ISSN:1075-2617