Phospholipid transfer protein mediated conversion of high density lipoproteins generates pre beta 1-HDL. 1996

A von Eckardstein, and M Jauhiainen, and Y Huang, and J Metso, and C Langer, and P Pussinen, and S Wu, and C Ehnholm, and G Assmann
Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, Germany.

High density lipoproteins (HDL) subclasses can be differentiated by two-dimensional non-denaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) and subsequent immunoblotting. The quantitatively minor HDL-subclasses pre beta 1-LpA-I and gamma-LpE are initial acceptors of cell-derived cholesterol into the plasma compartment. In this study we analysed the effect of phospholipid transfer protein (PLTP) on the electrophoretic distribution of HDL-subclasses in plasma as well as the ability of plasma, pre beta 1-LpA-I, and gamma-LpE to take up [3H]cholesterol from labeled fibroblasts. Pre beta 1-LpA-I but not gamma-LpE disappeared during a 16 hours incubation in the absence of PLTP. During a one minute incubation pre beta 1-LpA-I of pre-incubated plasma released 75% less [3H]cholesterol from radiolabeled fibroblasts than pre beta 1-LpA-I of control plasma. Pre-incubation of plasma reduced the uptake of [3H]cholesterol by gamma-LpE by 40%. Totally, the cholesterol efflux capacity of plasma decreased by 10% compared to the original sample. The amount of immunodetectable pre beta 1-LpA-I increased when plasma was incubated in the presence of PLTP while the amount of immunodetectable gamma-LpE did not change. After one minute incubation of PLTP-conditioned plasma with [3H]cholesterol-labeled fibroblasts, the amount of radioactive cholesterol taken up by pre beta 1-LpA-I was twice as high as in control plasma whereas the amount of [3H]cholesterol taken up by gamma-LpE remained unchanged. As a net result, treatment with PLTP increased the cholesterol efflux into total plasma by 40%. Together with results of previous studies our data suggest that the conversion of alpha-LpA-I3 into alpha-LpA-I2 by PLTP generates pre beta 1-LpA-I but not gamma-LpE. PLTP helps to enhance the uptake of cell-derived cholesterol by pre beta 1-LpA-I and, thereby, the cholesterol efflux capacity of normal plasma.

UI MeSH Term Description Entries
D008075 Lipoproteins, HDL A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases. High Density Lipoprotein,High-Density Lipoprotein,High-Density Lipoproteins,alpha-Lipoprotein,alpha-Lipoproteins,Heavy Lipoproteins,alpha-1 Lipoprotein,Density Lipoprotein, High,HDL Lipoproteins,High Density Lipoproteins,Lipoprotein, High Density,Lipoprotein, High-Density,Lipoproteins, Heavy,Lipoproteins, High-Density,alpha Lipoprotein,alpha Lipoproteins
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
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
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001057 Apolipoproteins E A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III. Apo-E,Apo E,Apo E Isoproteins,ApoE,Apolipoprotein E Isoproteins,Apoprotein (E),Apoproteins E,Isoproteins, Apo E,Isoproteins, Apolipoprotein E
D013631 Tangier Disease An autosomal recessively inherited disorder caused by mutation of ATP-BINDING CASSETTE TRANSPORTERS involved in cellular cholesterol removal (reverse-cholesterol transport). It is characterized by near absence of ALPHA-LIPOPROTEINS (high-density lipoproteins) in blood. The massive tissue deposition of cholesterol esters results in HEPATOMEGALY; SPLENOMEGALY; RETINITIS PIGMENTOSA; large orange tonsils; and often sensory POLYNEUROPATHY. The disorder was first found among inhabitants of Tangier Island in the Chesapeake Bay, MD. A-alphalipoprotein Neuropathy,Analphalipoproteinemia,Tangier Disease Neuropathy,Alpha High Density Lipoprotein Deficiency Disease,Cholesterol Thesaurismosis,HDLDT1,High Density Lipoprotein Deficiency, Tangier Type,High Density Lipoprotein Deficiency, Type 1,High-Density Lipoprotein Deficiency, Tangier Type,High-Density Lipoprotein Deficiency, Type I,Neuropathy of Tangier Disease,Tangier Hereditary Neuropathy,A-alphalipoprotein Neuropathies,Analphalipoproteinemias,Cholesterol Thesaurismoses,High Density Lipoprotein Deficiency, Type I,Neuropathies, A-alphalipoprotein,Neuropathy, A-alphalipoprotein,Thesaurismoses, Cholesterol,Thesaurismosis, Cholesterol
D015151 Immunoblotting Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies. Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings

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