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Selective uptake of cholesteryl esters from high-density lipoprotein-derived LpA-I and LpA-I:A-II particles by hepatic cells in culture. 1998

F Rinninger, and T Kaiser, and E Windler, and H Greten, and J C Fruchart, and G Castro
Universität Hamburg, Krankenhaus Eppendorf, Medizinische Kernklinik und Poliklinik, Hamburg, Germany.

Selective uptake of high-density lipoprotein (HDL)-associated cholesteryl esters (CE), i.e. lipid uptake independent of HDL particle uptake, delivers CE to the liver and steroidogenic tissues in vivo and in vitro. From human plasma HDL, two major subpopulations of particles can be isolated: one contains both apolipoprotein (apo) A-I and apo A-II (designated LpA-I:A-II) as dominant protein components, whereas in the other apo A-II is absent (LpA-I). In this study, selective CE uptake from LpA-I and LpA-I:A-II by cultured cells was investigated. LpA-I and LpA-I:A-II were isolated by immunoaffinity chromatography from human plasma high-density lipoprotein3 (HDL3, d = 1.125-1.21 g/ml) and both particles were radiolabeled in the protein (125I) as well as in the CE moiety ([3H]cholesteryl oleyl ether ([3H]CEt)). Several control experiments validated the labeling methodology applied. To investigate selective CE uptake, human Hep G2 hepatoma cells, human hepatocytes in primary culture and human skin fibroblasts were incubated in medium containing doubly radiolabeled LpA-I or LpA-I:A-II particles. Thereafter cellular tracer content was determined. For each cell type the rate of apparent lipoprotein particle uptake according to the lipid tracer ([3H]CEt) was in substantial excess over that due to the protein tracer (125I), demonstrating selective CE uptake from LpA-I as well as from LpA-I:A-II. This difference in uptake between [3H]CEt and 125I, i.e. the rate of apparent selective CE uptake, was significantly higher for LpA-I compared to LpA-I:A-II, and this was dose- as well as time-dependent. Thus in human hepatic cell and fibroblasts, CE are selectively taken up to a higher extent from LpA-I compared to LpA-I:A-II. These results may suggest that LpA-I particles of the human plasma HDL fraction may be those lipoproteins which more efficiently deliver CE to the liver via the selective uptake pathway whereas LpA-I:A-II may play a less important role.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
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
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002499 Centrifugation, Density Gradient Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Centrifugations, Density Gradient,Density Gradient Centrifugation,Density Gradient Centrifugations,Gradient Centrifugation, Density,Gradient Centrifugations, Density
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
D002846 Chromatography, Affinity A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014316 Tritium The radioactive isotope of hydrogen also known as hydrogen-3. It contains two NEUTRONS and one PROTON in its nucleus and decays to produce low energy BETA PARTICLES. Hydrogen-3,Hydrogen 3

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