Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis.
An electron spin probe study was made of the effect of lipid peroxidation (LPO) on the structure of surface proteolipid layer of human serum low-density lipoproteins (LDL). The results obtained with a positively charged spin label and stearic acid spin probes with doxyl labels at positions 5, 12, and 16 revealed that LPO caused a decrease in phospholipid molecule mobility both in the region of polar heads and in the region of acyl chains till the depth of at least 1.7 mm from water-lipid interface. Under relatively high levels of oxidation (more than 6 mumol MDA/g LDL phospholipid) the polarity of lipid phase increased. The decrease in efficiency of tryptophan fluorescence quenching by nitroxide fragments incorporated in hydrophobic regions at the depth of approximately 2 nm from water-lipid interface indicated that lipid-protein interaction was disturbed as a result of oxidation of LDL lipids. In addition, the LPO-induced modification of apo-B, the main protein of LDL, was examined with maleimide spin label. LPO led to increase in mobility of strongly immobilized maleimide labels and in the number of weakly immobilized ones. Oxidized LDL revealed decreased ability to incorporate spin-labeled steroid (androstane) as compared to native ones. LPO-induced structural changes of LDL surface are supposed to be a reason of enhanced accumulation of cholesterol in human monocytes during their incubation with oxidized LDL. The cholesterol content in red cells was shown to be directly correlated to MDA content in apo-B containing lipoproteins but not in whole serum. Our findings suggest that free radical modification of serum lipoproteins but not solely an increased level of LPO products in blood is one important cause for cholesterol accumulation in cells and, apparently, for their transformation into foam cells during atherosclerosis.
Panasenko
O M
OM
Research Institute of Physico-Chemical Medicine, Moscow, USSR.
Vol'nova
T V
TV
Azizova
O A
OA
Vladimirov
Y A
YA
D001161:Arteriosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000097:blood; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000378:metabolism; D005453:Fluorescence; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D013113:Spin Labels
D005609:Free Radicals; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D013113:Spin Labels; D008315:Malondialdehyde; D002784:Cholesterol