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Mechanisms of Oxidative Modification of Low Density Lipoproteins under Conditions of Oxidative and Carbonyl Stress

V. Z. Lankin1*, A. K. Tikhaze1, V. I. Kapel'ko1, G. S. Shepel'kova1, K. B. Shumaev2, O. M. Panasenko1, G. G. Konovalova1, and Yu. N. Belenkov1

1Russian Research Cardiology Complex, 3-ya Cherepkovskaya ul. 15a, 121552 Moscow, Russia; fax: (495) 414-6699; E-mail: lankin@cardio.ru

2Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky pr. 33, 119071 Moscow, Russia; fax: (495) 954-2732; E-mail: inbio@inbio.ras.ru

* To whom correspondence should be addressed.

Received May 4, 2007
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 Q10 is the most active lipid-soluble natural antioxidant, and suppression of ubiquinol Q10 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 Q10 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.
KEY WORDS: low density lipoproteins, lipid hydroperoxides, malonic dialdehyde, glyoxal, methylglyoxal, ubiquinone Q10, oxidative stress, carbonyl stress

DOI: 10.1134/S0006297907100069