Uptake of retinyl ester in HL-60 cells via the low-density-lipoprotein-receptor pathway

Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2-fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells.

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Hypercholesterolemia Due to Lipoprotein X: Case Report and Thematic Review

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/1179551419878687 ◽

2019 ◽

Vol 12 ◽

pp. 117955141987868 ◽

Cited By ~ 2

Author(s):

Laura Kattah ◽

Andrés Gómez ◽

Sebastián Gutiérrez ◽

Kathalina Puerto ◽

Eiman D Moreno-Pallares ◽

...

Keyword(s):

Total Cholesterol ◽

Low Density Lipoprotein ◽

Cholesterol Acyltransferase ◽

Ldl Receptor ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

Definitive Treatment ◽

Primary Biliary Cholangitis ◽

Low Density ◽

Hepatic Diseases

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.

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A study of the chylomicron metabolism in WHHL rabbits after fat loading. Discrepancy between results based on measurement of apoprotein B-48 or retinyl palmitate

Biochemical Journal ◽

10.1042/bj2850641 ◽

1992 ◽

Vol 285 (2) ◽

pp. 641-646 ◽

Cited By ~ 16

Author(s):

P N M Demacker ◽

P J van Heijst ◽

A F H Stalenhoef

Keyword(s):

New Zealand ◽

Strong Correlation ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Retinyl Palmitate ◽

Receptor Activity ◽

Low Density ◽

Apoprotein B ◽

Chylomicron Metabolism

We studied the metabolism of chylomicrons in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits and in cholesterol-fed or normally fed New Zealand White (NZW) rabbits by measuring the concentrations of apoprotein B-48 and of retinyl palmitate in their serum after feeding fat plus this vitamin according to two different protocols. Compared with NZW controls, retinyl palmitate accumulated in both hyperlipidaemic groups under study, not only in the d less than 1.019 fraction but also in the low-density lipoprotein (LDL) fraction. A strong correlation was found between the retinyl palmitate concentration in either the d less than 1.019 fraction or the LDL fraction of the WHHL rabbits and the concentrations of cholesterol and triacylglycerols in these fractions. This suggests that retinyl palmitate is exchanged rapidly between exogenous and endogenous lipoproteins. This is supported by the lack of a correlation between the retinyl palmitate concentrations and the intensity of the apoprotein B-48 band in the respective d less than 1.019 fractions or LDL fractions; in most fractions, in which large amounts of retinyl palmitate were present, the intensity of the apoprotein B-48 band was not increased compared with the fasting concentrations. Assuming that retinyl palmitate is a marker for the transfer of exogenous lipids, the results of our experiments indicate that the removal of exogenous lipids is delayed by complexing to endogenously synthesized lipoproteins. However, the clearance of apoprotein B-48 is normal and thus independent of the LDL-receptor activity.

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Differential antioxidative and hypocholesterolemic responses to two fish protein hydrolysates (Sardina pilchardus and Boops boops) in cholesterol-fed rats

Nutrition & Food Science ◽

10.1108/nfs-11-2014-0096 ◽

2015 ◽

Vol 45 (3) ◽

pp. 448-466 ◽

Cited By ~ 3

Author(s):

Souhila Benomar ◽

Sanaa Yahia ◽

Faiza Dehiba ◽

Natalia Guillen ◽

Maria Jesús Rodriguez-Yoldi ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Cholesterol Acyltransferase ◽

Density Lipoprotein ◽

Protein Hydrolysates ◽

Size Exclusion ◽

Control Group ◽

Low Density ◽

Acyltransferase Activity ◽

Content Type ◽

Male Wistar Rats

Purpose – The purpose of this study was to evaluate the antioxidant and hypocholesterolemic activities of sardine and bogue protein hydrolysates in cholesterol-fed rats. Design/methodology/approach – In total, 18 male Wistar rats (220 ± 10 g) fed 20 per cent casein, 1 per cent cholesterol and 0.5 per cent cholic acid were divided into three groups and received a daily gavage of 250 mg of sardine (SPH) or bogue (BPH) protein hydrolysates for 30 days. The third group, named control group (CG), received in the same conditions water. Lipoproteins were fractionated by size-exclusion fast protein liquid chromatography, and serum lipids, apolipoproteins and lipoproteins were assayed. Findings – In SPH and BPH groups, serum total cholesterol concentrations were −66 per cent lower than in CG. This corresponded to the decreased very low-density lipoprotein-C in the former groups. Moreover, BPH treatment reduced low-density lipoprotein-C compared with CG and SPH groups. Compared with CG, serum phospholipids were reduced by SPH and BPH. Furthermore, BPH increased significantly APOA4 and sphingomyelin but lowered phosphatidylcholine. In the latter group, serum lecithin cholesterol acyltransferase activity was +23 per cent higher, but with SPH, this activity was −35 per cent reduced compared with CG. Apolipoprotein A-I contents were similar in the three groups. Compared with CG, hydroperoxide and lipid peroxidation contents in serum and lipoprotein fractions were reduced by SPH and BPH. Compared with CG, serum superoxide dismutase and glutathione peroxidase activities were increased in the treated groups, particularly in the BPH group. Originality/value – These results suggest that sardine protein hydrolysates and particularly those of bogue could be a very useful natural compound to prevent hypercholesterolemia by both improving the lipid profile and modulating oxidative stress in cholesterol-fed rats.

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The human asialoglycoprotein receptor is a possible binding site for low-density lipoproteins and chylomicron remnants

Biochemical Journal ◽

10.1042/bj2760079 ◽

1991 ◽

Vol 276 (1) ◽

pp. 79-87 ◽

Cited By ~ 38

Author(s):

E Windler ◽

J Greeve ◽

B Levkau ◽

V Kolb-Bachofen ◽

W Daerr ◽

...

Keyword(s):

Cell Density ◽

Hepg2 Cells ◽

High Cell Density ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Asialoglycoprotein Receptor ◽

Low Density ◽

High Cell ◽

Chylomicron Remnants

Binding and internalization of chylomicron remnants from rat mesenteric lymph by HepG2 cells was inhibited by both excess remnants and low-density lipoprotein (LDL) to the same extent. Ligand blots revealed binding of remnants and LDL to the LDL receptor. Measures regulating LDL receptor activity greatly influenced the binding of remnants: ethinyloestradiol, the hydroxymethylglutaryl-CoA reductase inhibitor pravastatin and the absence of LDL all increased binding, whereas high cell density or the presence of LDL decreased binding. Also, asialofetuin, asialomucin, the neoglycoprotein galactosyl-albumin and an antibody against the asialoglycoprotein receptor all decreased substantially the binding of remnants. At high cell density, binding internalization and degradation of chylomicron remnants was inhibited by up to 70-80%, yet binding of LDL was inhibited by no more than 20-30%. In cross-competition studies, the binding of 125I-asialofetuin was efficiently competed for by asialofetuin itself or by the antibody, and also by LDL and remnants, yet remnants displayed an approx. 100-fold higher affinity than LDL. Likewise, remnants of human triacylglycerol-rich lipoproteins and asialofetuin interfered with each others' binding to HepG2 cells or human liver membranes. It is concluded that the LDL receptor mediates the internalization of chylomicron remnants into hepatocytes depending on its activity, according to demand for cholesterol. Additionally, the asialoglycoprotein receptor may contribute to the endocytosis of LDL, but predominantly of chylomicron remnants.

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Serum Lipids, Lipoproteins, and Lipid Metabolizing Enzymes in Identical Twins Discordant for Obesity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.8.4998 ◽

1998 ◽

Vol 83 (8) ◽

pp. 2792-2799 ◽

Cited By ~ 10

Author(s):

Tapani Rönnemaa ◽

Jukka Marniemi ◽

Markku J. Savolainen ◽

Y. Antero Kesäniemi ◽

Christian Ehnholm ◽

...

Keyword(s):

Apolipoprotein E ◽

Visceral Fat ◽

Genetic Factors ◽

Hepatic Lipase ◽

Low Density Lipoprotein ◽

Cholesterol Acyltransferase ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Acyltransferase Activity

abstract Obesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P < 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P ≤ 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P < 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.

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