Biomedical subjects

D Y Hui

Publications and source records attributed to D Y Hui.

75 records · Page 5Linked to original sources

PubMedDate not supplied

Uptake of apolipoprotein E-containing high density lipoproteins by hepatic parenchymal cells.

Cholesterol-enriched, apolipoprotein E-containing high density lipoproteins (apo E HDLc), which were isolated from the plasma of cholesterol-fed dogs by using agarose column chromatography or ultracentrifugation, possessed essentially identical biochemical and metabolic characteristics. Radioiodinated (125I) apo E HDLc isolated by either method gave identical rates of clearance from the plasma, i.e., greater than 50% of the injected dose was cleared from the plasma within 5 to 10 minutes, principally by the liver. Detailed studies localizing apo E HDLc uptake to specific cell types within the liver were performed in both normal and cholesterol-fed rats. The validity of using the canine apo E HDLc in the rat was supported by observations of marked similarities in plasma clearance, i.e., a rapid acute phase of disappearance, and a near-quantitative hepatic uptake of lipoproteins in both species. Canine apo E HDLc (fluorescently labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine), which were injected into normal rats, appeared to be taken up primarily by parenchymal cells, as determined by fluorescence microscopy. Light microscopic autoradiography also revealed that the uptake of 125I apo E HDLc was principally carried out by parenchymal cells in rat liver. Likewise, the uptake of apo E HDLc by the liver of cholesterol-fed rats was extensively localized to parenchymal cells. An in situ, single-pass perfusion of a lobule of the liver of a normal dog with iodinated and fluorescently labeled apo E HDLc confirmed that the uptake of the lipoproteins was principally carried out by parenchymal cells. The plasma clearance of apo E HDLc by hepatic parenchymal cells, even in cholesterol-fed animals in which the apo B,E (LDL) receptors were markedly down-regulated (undetectable), suggests that the apo E receptor, presumably the remnant receptor, is localized in the parenchymal cells.

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PubMedDate not supplied

Apolipoprotein E-binding proteins isolated from dog and human liver.

Chylomicron remnant catabolism appears to be mediated by apolipoprotein (apo) E binding to hepatic lipoprotein receptors. Previously, the apo B,E(LDL) receptor and a unique apo E-binding protein (referred to as the apo E receptor) were isolated from solubilized canine and human livers. In the present study, the apo E-binding fraction was further characterized and found to contain at least three proteins, all of which bind apo E-containing lipoproteins with high affinity. The 56-kDa band was found to contain the alpha- and beta-subunits of F1-ATPase, presumably derived from mitochondrial membranes. In addition, an apo E-binding protein with an apparent Mr approximately equal to 59,000 was identified. The 59-kDa protein displays calcium-independent binding on ligand blots, but displays both calcium-dependent and -independent binding in assays performed with detergent-solubilized protein. The 59-kDa protein recognized lipid-free as well as lipid-bound apo E in ligand blots, and also bound apo E-2, apo E-3, and apo E-4 in a comparable way. Monoclonal antibodies produced against the 59-kDa protein did not react with the 56-kDa proteins. Normal human liver, as well as the liver of a patient lacking the apo B,E(LDL) receptor, possessed the 56-kDa and 59-kDa proteins. These data indicate that liver cells possess at least three proteins, in addition to the apo B,E(LDL) receptor, that bind apo E-containing lipoproteins with high affinity. The physiological role of these proteins in apo E metabolism remains to be determined.

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PubMedDate not supplied

Chylomicron remnant metabolism. Role of hepatic lipoprotein receptors in mediating uptake.

Chylomicron remnants are catabolized by the liver, and their uptake within this organ is mediated by the presence of apolipoprotein (apo) E on the surface of these particles. In addition to a receptor for low density lipoproteins (LDL), several lines of evidence suggest that a unique receptor, referred to as the chylomicron remnant or apo E receptor, may be involved in the uptake of these lipoproteins. A possible candidate for the apo E receptor was previously isolated by affinity chromatography and was shown to possess high-affinity binding to apo E-containing lipoproteins, including chylomicron remnants, but not to possess high-affinity binding to apo B-containing LDL. However, it is now known that this fraction contains at least three proteins, all of which bind apo E with high affinity. An Mr congruent to 56,000 fraction contains two proteins that have been identified as the alpha- and beta-subunits of mitochondrial F1-adenosine 5'-triphosphatase (F1-ATPase). Furthermore, purified F1-ATPase binds apo E-containing lipoproteins with high affinity. It is very unlikely that these proteins, presumably isolated from mitochondrial membranes, are involved in chylomicron remnant metabolism. An Mr congruent to 59,000 fraction contains a unique apo E-binding protein that is not an ATPase. This protein appears to be localized to the endoplasmic reticulum of liver cells, but it is unclear whether this protein plays a role in chylomicron remnant catabolism. Furthermore, a cDNA clone coding for a protein that is apparently distinct from the ATPase and the Mr congruent to 59,000 protein has been obtained from a lambda gt11 library.(ABSTRACT TRUNCATED AT 250 WORDS)

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