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Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency. 1995

N Sakai, and S Yamashita, and K Hirano, and M Ishigami, and T Arai, and K Kobayashi, and T Funahashi, and Y Matsuzawa
Second Department of Internal Medicine, Osaka University Medical School, Japan.

We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the polydisperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002788 Cholesterol Esters Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. Cholesterol Ester,Cholesteryl Ester,Cholesteryl Esters,Ester, Cholesterol,Ester, Cholesteryl,Esters, Cholesterol,Esters, Cholesteryl
D004591 Electrophoresis, Polyacrylamide Gel Electrophoresis in which a polyacrylamide gel is used as the diffusion medium. Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D005260 Female Females
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006023 Glycoproteins Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins. C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated

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