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The amylin peptide implicated in type 2 diabetes stimulates copper-mediated carbonyl group and ascorbate radical formation

Masad, Atef and Tabner, Brian J and Mayes, Jennifer and Allsop, David (2011) The amylin peptide implicated in type 2 diabetes stimulates copper-mediated carbonyl group and ascorbate radical formation. Free radical biology & medicine, 51 (4). pp. 869-875. ISSN 1873-4596

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Abstract

Human amylin (hA), which is toxic to islet β-cells, can self-generate H(2)O(2), and this process is greatly enhanced in the presence of Cu(II) ions. Here we show that carbonyl groups, a marker of oxidative modification, were formed in hA incubated in the presence of Cu(II) ions or Cu(II) ions plus H(2)O(2), but not in the presence of H(2)O(2) alone. Furthermore, under similar conditions (i.e., in the presence of both Cu(II) ions and H(2)O(2)), hA also stimulated ascorbate radical formation. The same observations concerning carbonyl group formation were made when the histidine residue (at position 18) in hA was replaced by alanine, indicating that this residue does not play a key role. In complete contrast to hA, rodent amylin, which is nontoxic, does not generate H(2)O(2), and binds Cu(II) ions only weakly, showed none of these properties. We conclude that the hA-Cu(II)/Cu(I) complex is redox active, with electron donation from the peptide reducing the oxidation state of the copper ions. The complex is capable of forming H(2)O(2) from O(2) and can also generate (•)OH via Fenton chemistry. These redox properties of hA can explain its ability to stimulate copper-mediated carbonyl group and ascorbate radical formation. The formation of reactive oxygen species from hA in this way could hold the key to a better understanding of the damaging consequences of amyloid formation within the pancreatic islets of patients with type 2 diabetes mellitus.

Item Type: Article
Journal or Publication Title: Free radical biology & medicine
Additional Information: Copyright © 2011 Elsevier Inc. All rights reserved.
Uncontrolled Keywords: Type 2 diabetes mellitus ; Human amylin ; Rodent amylin ; Reactive oxygen species ; Carbonyl group ; Copper ions ; Oxidation ; Free radicals
Subjects: UNSPECIFIED
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
Faculty of Science and Technology > Psychology
ID Code: 50803
Deposited By: ep_importer_pure
Deposited On: 07 Nov 2011 09:45
Refereed?: Yes
Published?: Published
Last Modified: 26 Mar 2013 15:59
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/50803

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