Journal Article

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Jesús R. Requena, Min-Xin Fu, Mahtab U. Ahmed, Alicia J. Jenkins, Timothy J. Lyons and Suzanne R. Thorpe

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 11, issue supp5, pages 48-53
Published in print January 1996 | ISSN: 0931-0509
e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/11.supp5.48
Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

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Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatographymass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product Nε-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound Nε-(l-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Keywords: Nε-(carboxymethyl)lysine; 4-hydroxy-nonenal; lipid peroxidation; malondialdehyde; metalcatalysed oxidation; oxidative stress; protein chemical modification

Journal Article.  0 words. 

Subjects: Nephrology

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