Mechanisms of oxidative modification of low density lipoproteins under conditions of oxidative and carbonyl stress.
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.
Lankin
V Z
VZ
Russian Research Cardiology Complex, 3-ya Cherepkovskaya ul. 15a, 121552 Moscow, Russia. lankin@cardio.ru.
Tikhaze
A K
AK
Kapel'ko
V I
VI
Shepel'kova
G S
GS
Shumaev
K B
KB
Panasenko
O M
OM
Konovalova
G G
GG
Belenkov
Yu N
YN
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002244:Carbon / Q000737:chemistry*; D003067:Coenzymes / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009200:Myocardial Contraction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000737:chemistry
D000975:Antioxidants; D003067:Coenzymes; D008055:Lipids; D008077:Lipoproteins, LDL; D014451:Ubiquinone; D002244:Carbon; C024989:coenzyme Q10; D010100:Oxygen