barrow-methionineregulates-2005.pdf (135.05 kB)
Methionine regulates copper/hydrogen peroxide oxidation products of Aβ
journal contribution
posted on 2005-01-01, 00:00 authored by F Ali, F Separovic, Colin BarrowColin Barrow, R Cherny, F Fraser, A Bush, C Masters, K BarnhamMetal-catalysed oxidation (MCO) may play a causative role in the pathogenesis of Alzheimer's disease (AD). Amyloid peptide (A), the major biomarker of AD, in the presence of copper ions reduces Cu2+ to Cu+ and catalyses the formation of H2O2 that subsequently induces radicals through Fenton chemistry. A is also subject to attack by free radicals, where the presence of Cu2+ in conjunction with H2O2 catalyses oxygenation, primarily at the methionine sulfur atom. This work investigates MCO of A, 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 A (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 A and may relate to changes in properties of the peptide following MCO.
History
Journal
Journal of peptide scienceVolume
11Issue
6Pagination
353 - 360Publisher
John Wiley & SonsLocation
Bognor Regis, EnglandPublisher DOI
ISSN
1075-2617Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2004, John Wiley & SonsUsage metrics
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