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I Tabas

Publications and source records attributed to I Tabas.

83 records · Page 5Linked to original sources
PubMed1986

Recognition of vesicular lipoproteins by the apolipoprotein B,E receptor of cultured fibroblasts.

Vesicular lipoproteins (e.g., lipoprotein-X) are found in plasma in cholestasis or following infusion of Intralipid or phospholipid. To investigate the metabolism of vesicular lipoproteins, we isolated them from the plasma of subjects with cholestasis or following chronic or single Intralipid infusion. Cholestasis and chronic Intralipid therapy were found to be associated with elevated plasma concentrations of apoE, as determined by radioimmunoassay. Vesicular lipoproteins purified from each of the three types of plasma contained apoE, as well as other proteins. In cholestasis, in which levels of apoE were up to five times normal, a major portion of the plasma apoE was on vesicular lipoproteins. Normalized for apoE content, all preparations of vesicular lipoproteins displaced 125I-labeled LDL from apoB,E receptors of cultured fibroblasts identically. This displacement was inhibited by monoclonal antibodies that block receptor binding of apoE. Vesicular lipoproteins containing 125I-labeled apoE were internalized and degraded by fibroblasts. Different preparations caused small losses or gains of cellular cholesterol, with appropriate stimulation or suppression of apoB,E receptors. Thus, vesicular lipoproteins contain apoE, and apoE mediates their interaction with the apoB,E receptor. Our results suggest that the catabolism of cholesterol-rich vesicular lipoproteins, formed during cholestasis or following infusions of Intralipid or phospholipid, may be receptor-mediated.

Antibodies, Monoclonal↗
PubMed1985

Unmodified low density lipoprotein causes cholesteryl ester accumulation in J774 macrophages.

Cholesteryl ester (CE)-loaded macrophages (foam cells) are a prominent feature of atherosclerotic plaques. Previous studies have shown that human monocytes or resident mouse peritoneal macrophages accumulate CE in response to low density lipoprotein (LDL) only when the LDL has been appropriately chemically modified. By contrast, we report here that J774 macrophages accumulate large amounts of CE when incubated with unmodified LDL. The CE is stored in oil red O-positive droplets, which have the typical appearance of foam cell inclusions by electron microscopy. The fatty acid moieties of the cellular CE are enriched in oleate unlike those of LDL-CE, which are enriched in linoleate, indicating that the LDL-CE undergoes hydrolysis and reesterification by acyl CoA:cholesterol acyltransferase. Studies with 125I-labeled LDL at both 4 degrees C and 37 degrees C indicate that the LDL is internalized by a specific receptor that has several characteristics in common with the apolipoprotein B/E (apo B/E) receptor. However, in comparison with fibroblasts, the LDL receptor and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity in J774 cells are relatively resistant to down-regulation by LDL or 25-hydroxycholesterol, leading to receptor-mediated CE storage. In addition, J774 cells appear to accumulate CE from LDL internalized by nonspecific means. Thus, macrophage-like cells can accumulate CE in response to unmodified LDL by both nonspecific and receptor-mediated processes.

Animals↗
PubMed1984

Mechanism of the association of HDL3 with endothelial cells, smooth muscle cells, and fibroblasts. Evidence against the role of specific ligand and receptor proteins.

Human plasma high-density lipoprotein-3 (HDL3) has been shown to bind to a variety of cells and tissues. In order to investigate the nature of HDL3-cell association, we studied the interaction of 125I-HDL3 with porcine aortic endothelial cells, rabbit aortic smooth muscle cells, and normal human skin fibroblasts. At 37 degrees C, 125I-HDL3 association with endothelial cells was nonsaturable. Furthermore, 60% protein digestion of HDL3 by trypsin (T-HDL3) actually increased its ability, on a protein weight basis, to associate with endothelial cells and to displace 125I-HDL3 from all three cell types. Synthetic phospholipid-cholesterol discs containing either apo-A-I or apo-A-II were equally effective in displacing 125I-HDL3 from endothelial cells, and phospholipid-cholesterol vesicles containing no protein also displaced 125I-HDL3 from endothelial cells. Neither lipid-free apo-HDL3 nor apo-T-HDL3 was able to competitively displace 125I-HDL3. The above competitive displacement data, when expressed on a protein weight basis, showed differences in the ability of the competitors to displace 125I-HDL3 from cells in the following order of effectiveness: discs greater than T-HDL3 greater than native HDL3. When these data were expressed on a surface lipid weight basis, all three competitors, as well as the lipid vesicles, were approximately normalized to a single competitive displacement curve. Studies on the nature of the cellular mediators of HDL3-cell association revealed that the cell surface sites were resistant to proteolytic treatment. Furthermore, both 125I-HDL3 and 125I-T-HDL3 association with fibroblasts preincubated with varying concentrations of cholesterol increased in parallel with the free cholesterol content of the cells; although cycloheximide blocked this increase in HDL3-cell association, cycloheximide also prevented the increase in cholesterol content of cholesterol-treated cells. We conclude that the association of HDL3 with the cell types studied is not mediated by specific ligand and receptor proteins but rather involves the interaction of cellular surface lipids, possibly cholesterol, with the surface lipids of HDL3.

Animals↗
PubMed1979

Purification and characterization of a rat liver Golgi alpha-mannosidase capable of processing asparagine-linked oligosaccharides.

Studies in intact cells have shown the following processing reaction to occur during Asn-linked oligosaccharide biosynthesis (M, mannose; GlcNAc, N-acetylglucosamine): Formula: (See Text) We have identified a rat liver Golgi enzyme which catalyzes this reaction in vitro. This alpha-mannosidase has been purified 3,000 to 6,000-fold by subcellular fractionation, Triton X-100 solubilization, and ion exchange and hydroxylapatite chromatography. The purified enzyme has a pH optimum between 6.0 and 6.5 and a Km between 17 and 100 microM for a processing intermediate. The enzyme shows specificity for alpha 1,2-linked mannose residues. Structural analysis of the in vitro reaction products reveal that specific intermediates are formed in the conversion of the (Man)9GlcNAc oligosaccharide to the (Man)5GlcNAc oligosaccharide. Heat inactivation studies are consistent with the possibility that one enzyme activity is responsible for this conversion. The alpha 1,2-specific mannosidase described here appears to be distinct from two other rat liver Golgi alpha-mannosidase activities based on differential substrate specificity, inhibitor susceptibility, and detergent extractability.

Animals↗
PubMed1978

The synthesis of complex-type oligosaccharides. I. Structure of the lipid-linked oligosaccharide precursor of the complex-type oligosaccharides of the vesicular stomatitis virus G protein.

The synthesis of the complex-type oligosaccharide unit of the vesicular stomatitis virus G protein is initiated by the en bloc transfer of a high molecular weight oligosaccharide from a lipid carrier to the nascent polypeptide. Following transfer the oligosaccharide is "processed" by removal of glucose and mannose residues and the sugars that constitute the outer branches of the complex-type oligosaccharide are added. The structure of the oligosaccharide moiety of the lipid-linked precursor has been elucidated in order to further define the steps involved in processing. Since it was not feasible to obtain adequate amounts of material for standard structural studies, most of the structural studies were performed on radiolabeled material, with radioactivity incorporated differentially into glucose, mannose, and N-acetylglucosamine. Based on endo-beta-N-acetylglucosaminidase CII digestion, alpha-mannosidase digestion, acetolysis, Smith periodate degradation, methylation analysis, and periodate oxidation, we propose the following structure for the oligosaccharide moiety of the lipid-linked oligosaccharide.

Carbohydrates↗