scholarly journals Lysophosphatidylcholine increases the secretion of cholesteryl ester-poor triacylglycerol-rich lipoproteins by CaCo-2 cells

1994 ◽  
Vol 304 (1) ◽  
pp. 35-42 ◽  
Author(s):  
F J Field ◽  
E Born ◽  
H Chen ◽  
S Murthy ◽  
S N Mathur
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Esterification ◽  
Ester Synthesis ◽  
Triacylglycerol Synthesis ◽  
Apoprotein B ◽  
Apob Synthesis ◽  
Mass Accumulation

To address the effect of lysophosphatidylcholine on triacylglycerol transport in intestine, CaCo-2 cells, grown on semipermeable supports, were incubated with lysophosphatidylcholine solubilized in 1 mM taurocholate. [14C]Palmitoyllysophosphatidylcholine was readily taken up and incorporated predominantly into cellular phospholipids, particularly phosphatidylcholine. Twenty-five percent of the label was found in triacylglycerols. Compared with labelled cellular phospholipids, labelled triacylglycerols were preferentially secreted. Lysophosphatidylcholine caused a profound decrease in cholesteryl ester synthesis and secretion, whereas cellular triacylglycerol mass and triacylglycerol synthesis and secretion were increased. The effect was more pronounced with oleoyllysophosphatidylcholine than with either palmitoyl- or stearyl-lysophosphatidylcholine. Lysophosphatidylcholine increased the secretion of immunoreactive and newly-synthesized apoprotein B (apoB) without altering the rate of apoB synthesis. Thus, luminal lysophosphatidylcholine and/or its uptake decreases cholesterol esterification and secretion, but increases triacylglycerol synthesis and secretion, triacylglycerol mass accumulation and the secretion of apoB by CaCo-2 cells.

Lipid synthesis in macrophages derived from the human cell line THP-1: modulation of the effects of native and oxidized chylomicron-remnant-like particles by oestrogen

2001 ◽  
Vol 101 (4) ◽  
pp. 403-413 ◽  
Author(s):  
Mariarosaria NAPOLITANO ◽  
Kelly V. BATT ◽  
Michael AVELLA ◽  
Elena BRAVO ◽  
Kathleen M. BOTHAM
Keyword(s):  
Cholesteryl Ester ◽  
Cell Line ◽  
Lipid Synthesis ◽  
Thiobarbituric Acid ◽  
Human Monocyte ◽  
Cholesterol Esterification ◽  
Chylomicron Remnant ◽  
Triacylglycerol Synthesis ◽  
Ester Formation ◽  
Chylomicron Remnants

The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that this is influenced by exposure of the cells to oestrogen, was investigated using the human monocyte cell line THP-1 and chylomicron-remnant-like particles containing human apolipoprotein E (CRLPs). Synthesis of the lipids was measured by the incorporation of [3H]oleate into cholesteryl ester and triacylglycerol. CRLPs (5-40μg of cholesterol/ml) containing either trilinolein or triolein as the triacylglycerol component caused a dose-dependent decrease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRLPs, the level of thiobarbituric acid-reactive substances was increased by 6.3-fold and 2.2-fold in particles containing trilinolein and triolein respectively. Furthermore, CRLPs containing oxidized trilinolein lost their ability to down-regulate cholesterol esterification, while CRLPs containing oxidized triolein did not. Both types of oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macrophages with 17β-oestradiol caused increases of approx. 94% and 34% in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated cells were abolished, however, when CRLPs (40μg of cholesterol/ml) were added to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholesterol esterification in oestrogen-treated cells by approx. 48%. These findings with CRLPs suggest that chylomicron remnants have significant effects on cholesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.

scholarly journals Phosphatidylcholine increases the secretion of triacylglycerol-rich lipoproteins by CaCo-2 cells

1996 ◽  
Vol 314 (2) ◽  
pp. 569-575 ◽  
Author(s):  
Satya N. MATHUR ◽  
Ella BORN ◽  
Shubha MURTHY ◽  
F. Jeffrey FIELD
Keyword(s):  
Cholesteryl Ester ◽  
Secretory Pathway ◽  
Cholesterol Acyltransferase ◽  
Lipid Synthesis ◽  
Brefeldin A ◽  
Mrna Levels ◽  
Ester Synthesis ◽  
Acyltransferase Activity ◽  
Apob Mrna ◽  
Triacylglycerol Synthesis

The regulation of lipid synthesis and secretion by phosphatidylcholine was investigated in CaCo-2 cells grown on semipermeable filters. In cells incubated with 1 mM taurocholate and 100–500 μM phosphatidylcholine, cholesteryl ester synthesis was decreased, triacylglycerol synthesis was increased modestly, whereas phospholipid synthesis was unaffected. Acyl-CoA–cholesterol acyltransferase activity was decreased secondary to a decrease in the substrate (cholesterol) supply. The basolateral secretion of newly synthesized triacylglycerol and triacylglycerol mass was significantly increased by phosphatidylcholine, whereas cellular triacylglycerol mass decreased. This effect was not specific for phosphatidylcholine as phosphatidylethanolamine and phosphatidylserine also increased the secretion of newly synthesized triacylglycerols. Dioleoylphosphatidylcholine was as effective as egg phosphatidylcholine in increasing triacylglycerol transport. Dipalmitoylphosphatidylcholine, in contrast, was without effect. Phosphatidylcholine also increased the basolateral secretion of apolipoprotein B (apoB) mass without altering apoB mRNA levels. Disruption of the Golgi apparatus by monensin or brefeldin A prevented the increase in apoB secretion by phosphatidylcholine. Compared with microsomes prepared from control cells, those from cells incubated with phosphatidylcholine contained more newly synthesized apoB. The percentage of new synthesized apoB isolated from the lumen of microsomes (as an estimate of apoB destined for secretion), however, was similar in the two preparations. Thus in CaCo-2 cells incubated with phosphatidylcholine, the transport of apoB and triacylglycerols is increased whereas cholesteryl ester synthesis and secretion are decreased. A normally functioning secretory pathway is required for phosphatidylcholine to increase triacylglycerol-rich lipoprotein secretion.

scholarly journals Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain

1997 ◽  
Vol 326 (1) ◽  
pp. 205-213 ◽  
Author(s):  
Thomas A. LAGACE ◽  
David M. BYERS ◽  
Harold W. COOK ◽  
Neale D. RIDGWAY
Keyword(s):  
Golgi Apparatus ◽  
Cholesteryl Ester ◽  
Chinese Hamster Ovary ◽  
Potential Role ◽  
Chinese Hamster ◽  
Cholesterol Esterification ◽  
Ester Synthesis ◽  
Ph Domain ◽  
Wild Type ◽  
Oxysterol Binding Protein

Oxysterol-binding protein (OSBP) is a high-affinity receptor for a variety of oxysterols, such as 25-hydroxycholesterol, that down-regulate cholesterol synthesis and stimulate cholesterol esterification. To examine a potential role for OSBP in regulating cholesterol metabolism, we stably overexpressed this protein in Chinese-hamster ovary (CHO)-K1 cells. Compared with mock-transfected controls, several cell lines overexpressing wild-type OSBP (CHO-OSBP) displayed a 50% decrease in cholesteryl ester synthesis when cultured in medium with delipidated serum, 25-hydroxycholesterol or low-density lipoprotein (LDL) . CHO-OSBP cells showed a 40–60% decrease in acyl-CoA:cholesterol acyltransferase activity and mRNA, a 50% elevation in mRNA for three sterol-regulated genes [LDL receptor, 3-hydroxy-3-methylgluraryl (HMG)-CoA reductase and HMG-CoA synthase], and an 80% increase in [14C]acetate incorporation into cholesterol. CHO-K1 cells overexpressing two OSBP mutants with a complete or N-terminal deletion of the pleckstrin homology (PH) domain had cholesterol esterification and synthesis rates that were similar to those shown by mock-transfected controls. Unlike wild-type OSBP, both PH domain mutants displayed diffuse cytoplasmic immunofluorescence staining and did not translocate to the Golgi apparatus in the presence of 25-hydroxycholesterol. CHO-K1 cells overexpressing OSBP have pronounced alterations in cholesterol esterification and synthesis, indicating a potential role for this receptor in cholesterol homoeostasis. The phenotype observed in cells overexpressing OSBP is dependent on the PH domain, which appears to be necessary for ligand-dependent localization of OSBP to the Golgi apparatus.

scholarly journals Regulation of the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages

1994 ◽  
Vol 301 (3) ◽  
pp. 675-681 ◽  
Author(s):  
P Vijayagopal
Keyword(s):  
Cholesteryl Ester ◽  
Conditioned Medium ◽  
Density Lipoprotein ◽  
Human Monocyte ◽  
Cholesterol Esterification ◽  
Human Aorta ◽  
Ester Synthesis ◽  
Fibrous Plaque

Studies were performed to evaluate the effect of several factors on the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages. In vivo apoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous-plaque lesions and low-density lipoprotein (LDL)-proteoglycan complex was formed in vitro. Degradation of LDL-proteoglycan complex and cholesteryl ester synthesis mediated by the in vivo and in vitro complexes were lowest in freshly isolated monocytes. With the maturation of monocytes into macrophages, there was a dramatic rise in both. The degradation of the complex and the resultant stimulation of cholesterol esterification increased significantly with increasing cell density. Preincubation of macrophages in medium containing lipoprotein cholesterol did not down-regulate the subsequent degradation of LDL-proteoglycan complex. Macrophage-conditioned medium had a profound stimulatory effect on the degradation of LDL-proteoglycan complex and cholesterol esterification by mature macrophages and freshly isolated monocytes. The conditioned medium lost its stimulatory activity after boiling, dialysis and trypsin digestion. Macrophage activation with phorbol ester and bacterial lipopolysaccharide resulted in a marked suppression of the binding and degradation of the complex, as well as the complex-mediated cholesteryl ester synthesis. These results demonstrate that several factors regulate the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages.

scholarly journals Plasma Cholesteryl Ester Transfer, But Not Cholesterol Esterification, Is Related to Lipoprotein-Associated Phospholipase A2: Possible Contribution to an Atherogenic Lipoprotein Profile

2011 ◽  
Vol 96 (4) ◽  
pp. 1077-1084 ◽  
Author(s):  
Robin P. F. Dullaart ◽  
Alexander Constantinides ◽  
Frank G. Perton ◽  
Jeroen J. J. van Leeuwen ◽  
Joost L. van Pelt ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Cholesteryl Ester ◽  
Apolipoprotein B ◽  
Density Lipoprotein ◽  
Activity Level ◽  
Cholesterol Esterification ◽  
Lcat Activity ◽  
Plasma Cholesteryl Ester ◽  
Diabetes Status ◽  
Atherogenic Lipoprotein Profile

Abstract Context: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol and small, dense low-density lipoproteins, is affected by the composition and concentration of apolipoprotein B-containing cholesteryl ester acceptor lipoproteins. Objective: We tested relationships of CET with Lp-PLA2 in subjects with and without metabolic syndrome (MetS). Design and Setting: In 68 subjects with MetS and 74 subjects without MetS, plasma Lp-PLA2 mass, cholesterol esterification (EST), lecithin:cholesterol acyltransferase (LCAT) activity level, CET, CET protein (CETP) mass, and lipoproteins were measured. Results: EST, LCAT activity, CET (P < 0.001 for all), and CETP (P = 0.030) were increased, and Lp-PLA2 was decreased (P = 0.043) in MetS. CET was correlated positively with Lp-PLA2 in subjects with and without MetS (P < 0.05 for both). EST and LCAT activity were unrelated to Lp-PLA2, despite a positive correlation between EST and CET (P < 0.001). After controlling for age, sex, and diabetes status, CET was determined by Lp-PLA2 in the whole group (β = 0.245; P < 0.001), and in subjects with (β = 0.304; P = 0.001) and without MetS (β = 0.244; P = 0.006) separately, independently of triglycerides and CETP. Conclusions: Plasma CET is related to Lp-PLA2 in subjects with and without MetS. The process of CET, but not EST, may be influenced by Lp-PLA2. These findings provide a rationale to evaluate whether maneuvers that inhibit Lp-PLA2 will reduce CET, and vice versa to document effects of CETP inhibition on Lp-PLA2.

scholarly journals The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

Inhibition of cholesterol esterification increases cholesteryl ester uptake from hdl in parental and mdr1 resistant ccrf-cem cells

2014 ◽  
Vol 235 (2) ◽  
pp. e301
Author(s):  
F. Angius ◽  
S. Uda ◽  
S. Spolitu ◽  
S. Deligia ◽  
S. Accossu ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Esterification
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