Turnbull, Stuart and Tabner, Brian J. and El-Agnaf, Omar M. A. and Twyman, Lance J. and Allsop, David (2001) New evidence that the Alzheimer β-amyloid peptide does not spontaneously form free radicals: An ESR study using a series of spin-traps. Free Radical Biology and Medicine, 30 (10). pp. 1154-1162. ISSN 0891-5849Full text not available from this repository.
The direct formation of free radicals from Aβ has been suggested to be a key neurotoxic mechanism in Alzheimer’s disease (AD). We have explored the possibility of the spontaneous formation of peptide-derived free radicals during the incubation of Aβ 1-40 by ESR spectroscopy using N-tert-butyl--phenylnitrone (PBN), 5,5-dimethyl-1-pyrroline N-oxide (DMPO), -(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), and 3,5-dibromo-4-nitrosobenzenesulfonic acid sodium salt (DBNBS) as spin traps. Employing PBN, we observed spectra during the incubation of β-amyloid peptide, at 37°C, which included adducts of 2-methyl-2-nitrosopropane (MNP), despite rigorous purification of the PBN before incubation. The formation of some of these adducts was found to be enhanced by ambient laboratory light. Our experiments have led us to propose a hypothesis that PBN undergoes hydrolysis and decomposition in the presence of oxidants, which explains the origin of all of the PBN and MNP adducts observed (even when the PBN is highly purified). Hydrogen peroxide, formed during incubation, could play a major role as an oxidant in these experiments. Of the other three spin traps, only DMPO gave (very weak) spectra, but these could be assigned to its hydroxyl radical adduct, formed as an artifact by the nucleophilic addition of water to DMPO, catalyzed by trace levels of iron ions. Thus, while spectra are observed during our experiments, none of them can be assigned to adducts of radicals derived from the peptide and, therefore, our data do not support the suggestion that radicals are spontaneously formed from β-amyloid peptide.
|Journal or Publication Title:||Free Radical Biology and Medicine|
|Uncontrolled Keywords:||Alzheimer’s disease ; β-amyloid ; spin-trapping ; free radicals ; oxidative stress ; ESR spectroscopy ; hydrogen peroxide|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Departments:||Faculty of Science and Technology > Lancaster Environment Centre|
Faculty of Science and Technology > Physics
Faculty of Health and Medicine > Biomedical & Life Sciences
|Deposited By:||Prof David Allsop|
|Deposited On:||15 May 2008 11:42|
|Last Modified:||26 Jul 2012 18:27|
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