Mechanisms of oxidative modification of low density lipoproteins under conditions of oxidative and carbonyl stress

Abstract

Low-molecular-weight aldehydes (glyoxal, methylglyoxal, 3-deoxyglucosone) generated on autooxidation of glucose under conditions of carbonyl stress react much more actively with amino groups of L-lysine and epsilon-amino groups of lysine residues of apoprotein B-100 in human blood plasma low density lipoproteins (LDL) than their structural analogs (malonic dialdehyde (MDA), 4-hydroxynonenal) resulting on free radical oxidation of lipids under conditions of oxidative stress. Glyoxal-modified LDL aggregate in the incubation medium with a significantly higher rate than LDL modified by MDA, and MDA-modified LDL are markedly more poorly absorbed by cultured human macrophages and significantly more slowly eliminated from the rat bloodstream upon intravenous injection. Studies on kinetics of free radical oxidation of rat liver membrane phospholipids have shown that ubiquinol Q(10) is the most active lipid-soluble natural antioxidant, and suppression of ubiquinol Q(10) biosynthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins) is accompanied by intensification of lipid peroxidation in rat liver biomembranes and in LDL of human blood plasma. Injection of ubiquinone Q(10) protects the human blood plasma LDL against oxidation and prevents oxidative stress-induced damages to rat myocardium. A unified molecular mechanism of atherogenic action of carbonyl-modified LDL in disorders of lipid and carbohydrate metabolism is discussed.

Interrelation between Malonyl Dialdehyde-Dependent Modification and Cholesterol Content in Low-Density Lipoproteins

“…The content of MDA-modifi ed LDL was elevated by 33% in hypercholesterolemic patients, but remained practically unchanged in probands with hypertriglyceridemia (Table 1). These data are consistent with the results of our previous experiments demonstrating the important role of LDL peroxidation in the pathogenesis of atherosclerosis and confi rm the assumption that disturbances in lipid metabolism during atherogenesis can contribute to activation of free radical processes [1,2].Published data suggest the existence of interrelations between atherosclerosis and elevated content of MDA-modifi ed LDL in blood plasma [6,7,10,11]. Our study revealed a strong positive correlation between the concentration of total CH or LDL CH and content of oxidized (MDA-modifi ed) LDL in blood plasma from probands (r=0.68 and 0.72, respectively; p<0.05; Figs.…”

Nutritional improvement of metabolic syndrome parameters in immature fructose-fed wild-type mice

“…'Dicarbonyl-free radicals' are a normal byproduct of metabolism, the formation of which is accelerated in diabetes (28), and is involved in diabetic complications. Thus, the rationale for employing polyphenolics such as procyanidins and reactive carbonyl quenching amino acids, such as arginine and lysine (29,30), was not only to improve individual biochemical markers, but also to prevent damage by excess serum sugar, thereby negating sugar free radicals and sequestering oxidative radicals.…”

Interplay Between Oxidative and Carbonyl Stresses: Molecular Mechanisms, Biological Effects and Therapeutic Strategies of Protection

“…Extremely reactive carbonyl compound is HNE which possesses electrophilic double bond, carbonyl and hydroxyl groups. However, such dialdehydes as GO, MGO, and 3-DG are much more active than HNE and MDA (Lankin et al, 2007). In addition, acrolein reacts with thiols 100-fold more rapidly than HNE (Witz, G. 1989.…”