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

  title={Mechanisms of oxidative modification of low density lipoproteins under conditions of oxidative and carbonyl stress},
  author={Vadim Z. Lankin and Alla K. Tikhaze and V. I. Kapel’ko and G. S. Shepel’kova and Konstantin B Shumaev and Oleg M. Panasenko and Galina G. Konovalova and Yu. N. Belenkov},
  journal={Biochemistry (Moscow)},
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 ε-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… 
Oxidative and carbonyl stress as a factors of the modification of proteins and DNA destruction in diabetes.
It is shown that in DM patients the level of oxLDL increases and the content of SH-groups in proteins and peptides of the blood plasma decreases, which indicates the development of oxidative stress.
The influence of glucose on free radical peroxidation of low density lipoproteins in vitro and in vivo
Therapy with the sugar-lowering drug metformin caused much higher inhibition of the in vivo LDL peroxidation in blood of patients with diabetes mellitus probably due to the decrease of methylglyoxal-dependent generation of superoxide anion radicals.
The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes
The administration of sugar-lowering drug metformin caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals.
Macrophages actively accumulate malonyldialdehyde-modified but not enzymatically oxidized low density lipoprotein
In this study, we show that low density lipoproteins (LDL) from human blood plasma which was oxidized by animal C-15 lipoxygenase is taken up by cultivated human macrophages with the same
Malonyldialdehyde and glyoxal act differently on low-density lipoproteins and endotheliocytes
This study compared the influence of both dicarbonyl compounds on low-density lipoproteins (LDL) and the membrane of endotheliocytes and found that MDA induced more pronounced changes in physical and chemical properties of LDL particles than GOX-modified LDL.
Superoxide formation as a result of interaction of L-lysine with dicarbonyl compounds and its possible mechanism
It has been shown that nonenzymatic generation of free radicals including superoxide anion radical takes place during the interaction of L-lysine with methylglyoxal — an intermediate of carbonyl stress — at different (including physiological) pH values.
Hypoosmotic hemolysis of erythrocytes by active carbonyl forms
The findings point to the possibility of the multidirectional effect of low-molecular-weight dicarbonyls with similar structures on the structure and function of biological membranes.
Malondialdehyde-modified low-density lipoproteins as biomarker for atherosclerosis
MDA-modified LDL estimation has a diagnostic accuracy and may be used as an independent biochemical marker for atherosclerosis in patients with postinfarct cardiosclerosis.
Cholesterol-rich low density lipoproteins are also more oxidized
Estimation of oxLDL/HDL ratio may be used as an independent biochemical marker for atherosclerosis.
N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
In conclusion, NAC failed to significantly improve bone architecture/geometry/mechanical properties in the authors' rat model of progressive CKD, and AGE levels in the bone were elevated in CKD animals and were reduced with NAC although this did not translate to a benefit in bone mechanical properties.


Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol.
  • R. Stocker, V. Bowry, B. Frei
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
Investigation of the temporal disappearance of natural antioxidants associated with human low density lipoprotein (LDL) in relation to the appearance of various classes of lipid hydroperoxides shows that ubiquinol-10 is much more efficient in inhibiting LDL oxidation than either lycopene, beta-carotene, or alpha-tocopherol.
Glycation and oxidation: a role in the pathogenesis of atherosclerosis.
  • T. Lyons
  • Biology, Chemistry
    The American journal of cardiology
  • 1993
Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein.
LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo and are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL.
Intensification of Free Radical Oxidation of Low-Density Lipoproteins in the Plasma of Patients with Ischemic Heart Disease Receiving beta-Hydroxy-beta-Methylglutaryl-Coenzyme A Reductase Inhibitor Cerivastatin and Inhibition of Low-Density Lipoprotein Peroxidation with Antioxidant Probucol
The data indicate that antioxidant agents should be used in combination with inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (hypolipidemic preparations) for the therapy of patients with coronary heart disease.
Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages.
It is hypothesize that one modification of LDL in vivo may result from malondialdehyde which is released from blood platelets or is produced by lipid peroxidation at the site of arterial injury.
Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver
The results indicate that β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.
Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant.
It is proposed that perodixation is propagated within lipoprotein particles by reaction of the vitamin E radical with polyunsaturated fatty acid moieties in the lipid, which explains how reagents which reduce the alpha-tocopheroxyl radical strongly inhibit lipid peroxidation in vitamin E-containing LDL.
Oxidation-induced aggregation of rabbit low-density lipoprotein by azo initiator.
The results indicated that the oxidation by AAPH can induce the aggregation of LDL and that the AO-LDL contribute to lipid accumulation into macrophages more than the MO- LDL.
Effect of Ubiquinone Q10 and Antioxidant Vitamins on Free Radical Oxidation of Phospholipids in Biological Membranes of Rat Liver
It can be expected that reduced ubiquinone Q10in vivo should produce a more pronounced protective effect due to activity of the system for bioregeneration of this natural antioxidant.