Adductome-based identification of biomarkers for lipid peroxidation

Abstract

Lipid peroxidation is an endogenous source of aldehydes that gives rise to covalent modification of proteins in various pathophysiological states. In this study, a strategy for the comprehensive detection and comparison of adducts was applied to find a biomarker for lipid peroxidation-modified proteins This adductome approach utilized liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) methods designed to detect the specific product ions from positively ionized adducts in a selected reaction monitoring mode. Using this procedure, we comprehensively analyzed lysine and histidine adducts generated in the oxidized low-density lipoproteins (LDL) and observed a prominent increase in several adducts, including a major lysine adduct. Based on the high resolution ESI-MS of the adduct and on the LC-ESI-MS/MS analysis of the synthetic adduct candidates, the major lysine adduct detected in the oxidized LDL was identified as -(8-carboxyoctanyl)lysine (COL). Strikingly, a significantly higher amount of COL was detected in the sera from atherosclerosis-prone mice and from patients with hyperlipidemia compared with the controls. These data not only offer structural insights into protein modification by lipid peroxidation products but also provide a platform for the discovery of biomarkers for human diseases.

Extremely low frequency electromagnetic field reduces oxidative stress during the rehabilitation of post-acute stroke patients

“…The most common free radical process in the cell is a chain lipid peroxidation involving the oxidation of polyunsaturated fatty acid residues, which are part of membrane phospholipids and lipoproteins. 29 Peroxidation products undergo further transformations into fragments of different lengths.…”

Glycolaldehyde is an endogenous source of lysine N-pyrrolation

“…Strikingly, the deficiency of apoE was associated with a significant increase in the IgG and IgM titers against GA-derived epitopes. The apoE-deficient mice exhibit evidence of the markedly increased covalent modification of lysine residues in proteins as assessed by the formation of a major lipid peroxidation-derived lysine adduct, N ε -(8-carboxyoctanyl)lysine, and autoantibodies to oxidized lipoproteins (3,24). The most likely scenario is that the deficiency of apoE accelerates the peroxidation of fatty acids, which may be associated with the accumulation of GA and GA-modified proteins, leading to the overproduction of the autoantibodies to the pyrrolated proteins.…”

Cholesterol secosterol aldehyde adduction and aggregation of Cu,Zn-superoxide dismutase: Potential implications in ALS

“…Neurodegenerative diseases are known to be associated with redox stress, which increases the production of lipid-derived electrophiles [47] , [48] . Among the targets of these reactive products, proteins are likely the most suceptible to covalent modifications because their nucleophilic residues are easily attacked by aldehydes and other electrophiles [49] , [50] , [51] . Cholesterol 5,6-secosterol aldehydes (Seco A and Seco B) have been detected in brain tissues of patients with Lewy body [17] and Alzyheimer's disease [20] .…”