Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans[S

Science.gov (United States)

Amiot, Marie Josèphe; Knol, Diny; Cardinault, Nicolas; Nowicki, Marion; Bott, Romain; Antona, Claudine; Borel, Patrick; Bernard, Jean-Paul; Duchateau, Guus; Lairon, Denis

2011-01-01

Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (−32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (−43%, PE meal vs. control; P < 0.0001) and plasma (−54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans. PMID:21482714

Effect of rapeseed oil derived plant sterol and stanol esters on atherosclerosis parameters in cholesterol challenged heterozygous Watanabe Heritable Hyperlipidemic rabbits

DEFF Research Database (Denmark)

Schrøder, Malene; Fricke, Christiane; Pilegaard, Kirsten

2009-01-01

Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma...... campestanol (P Feeding RSO sterol esters increased concentrations of plasma campesterol (P ... of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration...

Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy

NARCIS (Netherlands)

Beentjes, JAM; Van Tol, A; Sluiter, WJ; Dullaart, RPF

Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein

Separating the mechanism-based and off-target actions of cholesteryl ester transfer protein inhibitors with CETP gene polymorphisms

NARCIS (Netherlands)

Sofat, Reecha; Hingorani, Aroon D.; Smeeth, Liam; Humphries, Steve E.; Talmud, Philippa J.; Cooper, Jackie; Shah, Tina; Sandhu, Manjinder S.; Ricketts, Sally L.; Boekholdt, S. Matthijs; Wareham, Nicholas; Khaw, Kay Tee; Kumari, Meena; Kivimaki, Mika; Marmot, Michael; Asselbergs, Folkert W.; van der Harst, Pim; Dullaart, Robin P. F.; Navis, Gerjan; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Thompson, John F.; McCaskie, Pamela; Palmer, Lyle J.; Arca, Marcello; Quagliarini, Fabiana; Gaudio, Carlo; Cambien, François; Nicaud, Viviane; Poirer, Odette; Gudnason, Vilmundur; Isaacs, Aaron; Witteman, Jacqueline C. M.; van Duijn, Cornelia M.; Pencina, Michael; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Ordovas, Jose; Li, Tricia Y.; Kakko, Sakari; Kauma, Heikki; Savolainen, Markku J.; Kesäniemi, Y. Antero; Sandhofer, Anton; Paulweber, Bernhard; Sorli, Jose V.; Goto, Akimoto; Yokoyama, Shinji; Okumura, Kenji; Horne, Benjamin D.; Packard, Chris; Freeman, Dilys; Ford, Ian; Sattar, Naveed; McCormack, Valerie; Lawlor, Debbie A.; Ebrahim, Shah; Smith, George Davey; Kastelein, John J. P.; Deanfield, John; Casas, Juan P.

2010-01-01

BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the

Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

NARCIS (Netherlands)

Sofat, Reecha; Hingorani, Aroon D.; Smeeth, Liam; Humphries, Steve E.; Talmud, Philippa J.; Cooper, Jackie; Shah, Tina; Sandhu, Manjinder S.; Ricketts, Sally L.; Boekholdt, S. Matthijs; Wareham, Nicholas; Khaw, Kay Tee; Kumari, Meena; Kivimaki, Mika; Marmot, Michael; Asselbergs, Folkert W.; van der Harst, Pim; Dullaart, Robin P. F.; Navis, Gerjan; van Veldhuisen, Dirk J.; Van Gilst, Wiek H.; Thompson, John F.; McCaskie, Pamela; Palmer, Lyle J.; Arca, Marcello; Quagliarini, Fabiana; Gaudio, Carlo; Cambien, Francois; Nicaud, Viviane; Poirer, Odette; Gudnason, Vilmundur; Isaacs, Aaron; Witteman, Jacqueline C. M.; van Duijn, Cornelia M.; Pencina, Michael; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Ordovas, Jose; Li, Tricia Y.; Kakko, Sakari; Kauma, Heikki; Savolainen, Markku J.; Kesaniemi, Y. Antero; Sandhofer, Anton; Paulweber, Bernhard; Sorli, Jose V.; Goto, Akimoto; Yokoyama, Shinji; Okumura, Kenji; Horne, Benjamin D.; Packard, Chris; Freeman, Dilys; Ford, Ian; Sattar, Naveed; McCormack, Valerie; Lawlor, Debbie A.; Ebrahim, Shah; Smith, George Davey; Kastelein, John J. P.; Deanfield, John; Casas, Juan P.

2010-01-01

Background-Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive

Effect of growth hormone replacement therapy on plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

NARCIS (Netherlands)

Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, We unknown. We carried out a 6 mouths study in 24

Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

DEFF Research Database (Denmark)

Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten

2009-01-01

Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged...... with dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...... and at termination, also in lipoproteins. Aortic atherosclerosis was evaluated as cholesterol content and area covered by plaque. Plasma cholesterol was not significantly different between the groups at termination (35.7 mmol/L vs. 35.5 mmol/L). A significant increase in LDL was seen (13.1 mmol/L vs. 16.5 mmol...

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Science.gov (United States)

Musolino, V; Gliozzi, M; Carresi, C; Maiuolo, J; Mollace, R; Bosco, F; Scarano, F; Scicchitano, M; Maretta, A; Palma, E; Iannone, M; Morittu, V M; Gratteri, S; Muscoli, C; Fini, M; Mollace, V

2017-01-01

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

NARCIS (Netherlands)

Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

2008-01-01

Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

Energy Technology Data Exchange (ETDEWEB)

Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.; (UTSMC)

2010-09-21

LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

Effect of 17alpha-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

International Nuclear Information System (INIS)

Nikitin, Yu.P.; Dushkin, M.I.; Dolgov, A.V.; Gordienko, I.A.

1987-01-01

Administration of estrogens is known to lower the concentration of cholesterol esters in the blood vessel wall and may delay the development of arteriosclerosis. It is also known that under the influence of estrogens the redistribution of concentrations of free cholesterol and cholesterol esters takes place in rats between the blood and liver as a result of the intensification of receptor-dependent uptake of low-density lipoproteins by the hepatocytes. The mechanisms of this intracellular redistribution, however, have been inadequately studied. The purpose of this paper is to study the effects of 17alpha-ethinylestradiol on the activity of lysosomal and cytoplasmic cholesterol esterases, acyl-CoA-cholesterol-O-acyltransferase, lysosomal acid phosphatase, and beta-D-galactosidase. The activity was measured by using cholesterol [1-C 14]-oleate as the substrate. The influence of the estradiol is found to be based on cholesterol redistribution between the blood and liver. Accumulation of free cholesterol in the liver under these conditions stimulates bile acid formation. Depression of cholesterol ester synthesis as a result of direct inhibition of the acyltransferase by the estradiol is found to possibly contribute to the fall in the cholesterol level in the body. Liquid scintillation counting was used to measure distribution and accumulation

How anacetrapib inhibits the activity of the cholesteryl ester transfer protein? Perspective through atomistic simulations.

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Tarja Äijänen

2014-11-01

Full Text Available Cholesteryl ester transfer protein (CETP mediates the reciprocal transfer of neutral lipids (cholesteryl esters, triglycerides and phospholipids between different lipoprotein fractions in human blood plasma. A novel molecular agent known as anacetrapib has been shown to inhibit CETP activity and thereby raise high density lipoprotein (HDL-cholesterol and decrease low density lipoprotein (LDL-cholesterol, thus rendering CETP inhibition an attractive target to prevent and treat the development of various cardiovascular diseases. Our objective in this work is to use atomistic molecular dynamics simulations to shed light on the inhibitory mechanism of anacetrapib and unlock the interactions between the drug and CETP. The results show an evident affinity of anacetrapib towards the concave surface of CETP, and especially towards the region of the N-terminal tunnel opening. The primary binding site of anacetrapib turns out to reside in the tunnel inside CETP, near the residues surrounding the N-terminal opening. Free energy calculations show that when anacetrapib resides in this area, it hinders the ability of cholesteryl ester to diffuse out from CETP. The simulations further bring out the ability of anacetrapib to regulate the structure-function relationships of phospholipids and helix X, the latter representing the structural region of CETP important to the process of neutral lipid exchange with lipoproteins. Altogether, the simulations propose CETP inhibition to be realized when anacetrapib is transferred into the lipid binding pocket. The novel insight gained in this study has potential use in the development of new molecular agents capable of preventing the progression of cardiovascular diseases.

Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

Science.gov (United States)

Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

2014-04-27

The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters.

Science.gov (United States)

Ash, Mark M; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

2011-07-01

The dietary impact of specific phytosterols incorporated into phytosterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytosterol esters containing different sterol moieties (sitosterol, sitostanol, or stigmasterol) but the same fatty acid moiety (stearic acid) produce different effects on cholesterol metabolism. Male Syrian hamsters were fed sitosterol, sitostanol, and stigmasterol stearate esters (25 g/kg diet) in an atherogenic diet containing cholesterol (1.2 g/kg) and coconut oil (80 g/kg). The phytosterol stearates produced no decrease in cholesterol absorption or plasma non-high-density lipoprotein cholesterol despite a reduction in liver free cholesterol in hamsters fed both sitosterol and sitostanol stearate diets. In addition, sitosterol stearate significantly increased fecal esterified and total neutral sterol excretion. Stigmasterol stearate did not differ from control in neutral sterol excretion, plasma lipids, or hepatic lipid concentration. Sitosterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmasterol stearate equivalently demonstrated the lowest. The cholesterol-lowering effect in liver-but not plasma-and the limited presence of fecal free sterols indicate that intact (unhydrolyzed) phytosterol stearates may impact cholesterol metabolism by mechanisms unrelated to the role of free phytosterols. The consumption of phytosterol esters at 2.5% of the diet elicited only modest impacts on cholesterol metabolism, although sitosterol stearate had a slightly greater therapeutic impact by lowering liver free cholesterol and increasing esterified and total neutral sterol fecal excretion, possibly due to a greater level of intestinal hydrolysis. Copyright © 2011 Elsevier Inc. All rights reserved.

An innovative method to selectively ablate cholesterol esters from an arteriosclerotic region of the arterial wall using a free-electron laser

International Nuclear Information System (INIS)

Awazu, K.; Nagai, A.; Tomimasu, T.; Aizawa, K.

1998-01-01

The selective removal of cholesterol esters accumulated in the intra-cellular or extra-cellular spaces has clinical significance. In the present work we investigate the removal of cholesterol esters by using a free electron laser (FEL) in an arteriosclerotic region. Thin films of cholesteryl oleate and albumin, and the cross-section of a rabbit artery were placed on an inverted microscope stage and the changes caused by the FEL irradiation of 5.75 and 6.1 μm with 1.5-3 mW in average were monitored continuously by a CCD camera in real time. FEL irradiation at a wavelength of 5.75 μm, which is a stretching vibrational mode of the ester, was able to ablate cholesterol esters without affecting albumin and that it can also remove cholesterol esters from rabbits' arteriosclerotic arterial walls. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Cholesterol transfer at endosomal-organelle membrane contact sites.

Science.gov (United States)

Ridgway, Neale D; Zhao, Kexin

2018-06-01

Cholesterol is delivered to the limiting membrane of late endosomes by Niemann-Pick Type C1 and C2 proteins. This review summarizes recent evidence that cholesterol transfer from endosomes to the endoplasmic reticulum and other organelles is mediated by lipid-binding proteins that localize to membrane contact sites (MCS). LDL-cholesterol in the late endosomal/lysosomes is exported to the plasma membrane, where most cholesterol resides, and the endoplasmic reticulum, which harbors the regulatory complexes and enzymes that control the synthesis and esterification of cholesterol. A major advance in dissecting these cholesterol transport pathways was identification of frequent and dynamic MCS between endosomes and the endoplasmic reticulum, peroxisomes and plasma membrane. Positioned at these MCS are members of the oxysterol-binding protein (OSBP) and steroidogenic acute regulatory protein-related lipid-transfer family of lipid transfer proteins that bridge the opposing membranes and directly or indirectly mediate cholesterol transfer. OSBP-related protein 1L (ORP1L), ORP5 and ORP6 mediate cholesterol transfer to the endoplasmic reticulum that regulates cholesterol homeostasis. ORP1L and STARD3 also move cholesterol from the endoplasmic reticulum-to-late endosomal/lysosomes under low-cholesterol conditions to facilitate intraluminal vesicle formation. Cholesterol transport also occurs at MCS with peroxisomes and possibly the plasma membrane. Frequent contacts between organelles and the endo-lysosomal vesicles are sites for bidirectional transfer of cholesterol.

Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases

Directory of Open Access Journals (Sweden)

Shinkai H

2012-05-01

Full Text Available Hisashi ShinkaiCentral Pharmaceutical Research Institute, JT Inc, Osaka, JapanAbstract: Elevated low-density lipoprotein (LDL cholesterol and lowered high-density lipoprotein (HDL cholesterol are important risk factors for cardiovascular disease. Accordingly, raising HDL cholesterol induced by cholesteryl ester transfer protein (CETP inhibition is an attractive approach for reducing the residual risk of cardiovascular events that persist in many patients receiving low-density LDL cholesterol-lowering therapy with statins. The development of torcetrapib, a CETP inhibitor, was terminated due to its adverse cardiovascular effects. These adverse effects did not influence the mechanism of CETP inhibition, but affected the molecule itself. Therefore a CETP modulator, dalcetrapib, and a CETP inhibitor, anacetrapib, are in Phase III of clinical trials to evaluate their effects on cardiovascular outcomes. In the dal-VESSEL (dalcetrapib Phase IIb endothelial function study and the dal-PLAQUE (safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging clinical studies, dalcetrapib reduced CETP activity by 50% and increased HDL cholesterol levels by 31% without changing LDL cholesterol levels. Moreover, dalcetrapib was associated with a reduction in carotid vessel-wall inflammation at 6 months, as well as a reduced vessel-wall area at 24 months compared with the placebo. In the DEFINE (determining the efficacy and tolerability of CETP inhibition with anacetrapib clinical study, anacetrapib increased HDL cholesterol levels by 138% and decreased LDL cholesterol levels by 36%. In contrast with torcetrapib, anacetrapib had no adverse cardiovascular effects. The potential of dalcetrapib and anacetrapib in the treatment of cardiovascular diseases will be revealed by two large-scale clinical trials, the dal-OUTCOMES (efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome study and the

Angiogenin activates phospholipase C and elicits a rapid incorporation of fatty acid into cholesterol esters in vascular smooth muscle cells

International Nuclear Information System (INIS)

Moore, F.; Riordan, J.F.

1990-01-01

Angiogenin activates the phosphoinositide-specific phospholipase C (PLC) in cultured rat aortic smooth muscle cells to yield a transient (30 s) peak of 1,2-diacylglycerol (DG) and inositol trisphosphate. Within 1 min, the DG level falls below that of the control and remains so for at least 20 min. A transient increase in monoacylglycerol indicates that depletion of DG may be the consequence of hydrolysis by DG lipase. In addition to these changes in second messengers, a rapid increase in incorporating of radiolabeled tracer into cellular cholesterol esters is observed. Stimulated cholesterol ester labeling is inhibited by preincubation with either the DG lipase inhibitor RHC 80267 or the acyl coenzyme A:cholesterol acyltransferase inhibitor Sandoz 58035. Cells prelabeled with [ 3 H]arachidonate show a sustained increase in labeling of cholesterol esters following exposure to angiogenin. In contrast, cells prelabeled with [ 3 H]oleate show only a transient elevation that returns to the basal level by 5 min. This suggests initial cholesterol esterification by oleate followed by arachidonate that is released by stimulation of the PLC/DG lipase pathway

Metabolism of cholesteryl esters of rat very low density lipoproteins.

Science.gov (United States)

Faergeman, O; Havel, R J

1975-06-01

Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent.

Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

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Fourgeux Cynthia

2015-03-01

Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

Free cholesterol is a potent regulator of lipid transfer protein function

International Nuclear Information System (INIS)

Morton, R.E.

1988-01-01

This study investigates the effect of altered lipoprotein free cholesterol (FC) content on the transfer of cholesteryl ester (CE) and triglyceride (TG) from very low- (VLDL), low- (LDL), and high-(HDL) density lipoproteins by the plasma-derived lipid transfer protein (LTP). The FC content of VLDL and HDL was selectively altered by incubating these lipoproteins with FC/phospholipid dispersions of varying composition. FC-modified lipoproteins were then equilibrated with [3H] TG, [14C]CE-labeled lipoproteins of another class to facilitate the subsequent modification of the radiolabeled donor lipoproteins. LTP was added and the extent of radiolabeled TG and CE transfer determined after 1 h. With either LDL or VLDL as lipid donor, an increase in the FC content of these lipoproteins caused a concentration-dependent inhibition (up to 50%) of CE transfer from these particles, without any significant effect on TG transfer. In contrast, with HDL as donor, increasing the HDL FC content had little effect on CE transfer from HDL, but markedly stimulated (up to 2.5-fold) the transfer of TG. This differential effect of FC on the unidirectional transfer of radiolabeled lipids from VLDL and HDL led to marked effects on LTP-facilitated net mass transfer of lipids. During long-term incubation of a constant amount of LTP with FC-modified VLDL and HDL, the extent of net mass transfer was linearly related to lipoprotein FC content; a 4-fold increase in FC content resulted in a 3-fold stimulation of the CE mass transferred to VLDL, which was coupled to an equimolar, reciprocal transfer of TG mass to HDL. Since lipid transfer between lipoproteins is integral to the process of reverse cholesterol transport, we conclude that lipoprotein FC levels are a potent, positive regulator of the pathways involved in sterol clearance. FC may modulate lipid transfer by altering the availability of CE and TG to LTP at the lipoprotein surface

Plant sterol ester diet supplementation increases serum plant sterols and markers of cholesterol synthesis, but has no effect on total cholesterol levels.

Science.gov (United States)

Weingärtner, Oliver; Bogeski, Ivan; Kummerow, Carsten; Schirmer, Stephan H; Husche, Constanze; Vanmierlo, Tim; Wagenpfeil, Gudrun; Hoth, Markus; Böhm, Michael; Lütjohann, Dieter; Laufs, Ulrich

2017-05-01

This double-blind, randomized, placebo-controlled, cross-over intervention-study was conducted in healthy volunteers to evaluate the effects of plant sterol ester supplemented margarine on cholesterol, non-cholesterol sterols and oxidative stress in serum and monocytes. Sixteen volunteers, average age 34 years, with no or mild hypercholesterolemia were subjected to a 4 week period of daily intake of 3g plant sterols per day supplied via a supplemented margarine on top of regular eating habits. After a wash-out period of one week, volunteers switched groups. Compared to placebo, a diet supplementation with plant sterols increased serum levels of plant sterols such as campesterol (+0.16±0.19mg/dL, p=0.005) and sitosterol (+0.27±0.18mg/dL, psynthesis such as desmosterol (+0.05±0.07mg/dL, p=0.006) as well as lathosterol (+0.11±0.16mg/dL, p=0.012). Cholesterol serum levels, however, were not changed significantly (+18.68±32.6mg/dL, p=0.052). These findings could not be verified in isolated circulating monocytes. Moreover, there was no effect on monocyte activation and no differences with regard to redox state after plant sterol supplemented diet. Therefore, in a population of healthy volunteers with no or mild hypercholesterolemia, consumption of plant sterol ester supplemented margarine results in increased concentrations of plant sterols and cholesterol synthesis markers without affecting total cholesterol in the serum, activation of circulating monocytes or redox state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat.

Science.gov (United States)

Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong

2017-03-22

Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a

Serum Cholesterol Reduction Efficacy of Biscuits with Added Plant Stanol Ester

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Wantanee Kriengsinyos

2015-01-01

Full Text Available This study’s aim was to test the low-density lipoprotein cholesterol- (LDL-c- lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study’s end. Compared to the control, the total cholesterol (TC, LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05. A significantly higher reduction in LDL-c (8.9% and LDL/HDL ratio (11.4% was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet.

Lecithin-cholesterol acyltransferase (LCAT) catalyzes transacylation of intact cholesteryl esters. Evidence for the partial reversal of the forward LCAT reaction

International Nuclear Information System (INIS)

Sorci-Thomas, M.; Babiak, J.; Rudel, L.L.

1990-01-01

Lecithin-cholesterol acyltransferase (LCAT) catalyzes the intravascular synthesis of lipoprotein cholesteryl esters by converting cholesterol and lecithin to cholesteryl ester and lysolecithin. LCAT is unique in that it catalyzes sequential reactions within a single polypeptide sequence. In this report we find that LCAT mediates a partial reverse reaction, the transacylation of lipoprotein cholesteryl oleate, in whole plasma and in a purified, reconstituted system. As a result of the reverse transacylation reaction, a linear accumulation of [3H]cholesterol occurred during incubations of plasma containing high density lipoprotein labeled with [3H]cholesteryl oleate. When high density lipoprotein labeled with cholesteryl [14C]oleate was also included in the incubation the labeled fatty acyl moiety remained in the cholesteryl [14C]oleate pool showing that the formation of labeled cholesterol did not result from hydrolysis of the doubly labeled cholesteryl esters. The rate of release of [3H]cholesterol was only about 10% of the forward rate of esterification of cholesterol using partially purified human LCAT and was approximately 7% in whole monkey plasma. Therefore, net production of cholesterol via the reverse LCAT reaction would not occur. [3H]Cholesterol production from [3H]cholesteryl oleate was almost completely inhibited by a final concentration of 1.4 mM 5,5'-dithiobis(nitrobenzoic acid) during incubation with either purified LCAT or whole plasma. Addition of excess lysolecithin to the incubation system did not result in the formation of [14C]oleate-labeled lecithin, showing that the reverse reaction found here for LCAT was limited to the last step of the reaction. To explain these results we hypothesize that LCAT forms a [14C]oleate enzyme thioester intermediate after its attack on the cholesteryl oleate molecule

Patient considerations and clinical impact of cholesteryl ester transfer protein inhibitors in the management of dyslipidemia: focus on anacetrapib

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Miyares MA

2012-08-01

Full Text Available Marta A Miyares, Kyle DavisPharmacy Department, Jackson Memorial Hospital, Miami, FL, USAAbstract: Cardiovascular disease (CVD is responsible for significant morbidity and mortality within the United States and worldwide. Although targeting low-density lipoprotein cholesterol (LDL-C in the prevention of CVD has been shown to be effective, evidence exists to indicate that significant cardiovascular (CV risk remains in patients receiving 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins – a risk that may be correlated with low levels of high-density lipoprotein cholesterol (HDL-C. Among the various tactics under investigation to increase HDL-C, inhibition of cholesteryl ester transfer protein (CETP appears the most adept to raise these levels. Although torcetrapib, a CETP inhibitor, demonstrated significant beneficial changes in HDL-C and LDL-C after 12 months of therapy when coadministered with atorvastatin, patients in the torcetrapib arm experienced a rise in mortality, including increased risk of death from CV and non-CV causes as well as a significant rise in major CV events. Later studies established that the adverse effects of torcetrapib were produced from molecule-specific off-target effects and not to the mechanism of CETP inhibition. These untoward outcomes have not been detected with anacetrapib, the third of the CETP inhibitors to enter Phase III trials. Furthermore, treatment with anacetrapib revealed both a statistically significant decrease in LDL-C and increase in HDL-C over placebo. While the place in therapy of niacin and fibrates to reduce CV events is currently in question secondary to the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes and the Action to Control CV Risk in Diabetes trials, the ongoing large-scale, randomized–placebo, controlled-outcomes study with anacetrapib coadministered with statin treatment will not

Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

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Laitinen Kirsi

2012-10-01

Full Text Available Abstract Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for

Increased large VLDL particles confer elevated cholesteryl ester transfer in diabetes

NARCIS (Netherlands)

Dullaart, Robin P. F.; de Vries, Rindert; Kwakernaak, Arjan J.; Perton, Frank; Dallinga-Thie, Geesje M.

BackgroundPlasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to

Rethinking reverse cholesterol transport and dysfunctional high-density lipoproteins.

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Gillard, Baiba K; Rosales, Corina; Xu, Bingqing; Gotto, Antonio M; Pownall, Henry J

2018-04-12

Human plasma high-density lipoprotein cholesterol concentrations are a negative risk factor for atherosclerosis-linked cardiovascular disease. Pharmacological attempts to reduce atherosclerotic cardiovascular disease by increasing plasma high-density lipoprotein cholesterol have been disappointing so that recent research has shifted from HDL quantity to HDL quality, that is, functional vs dysfunctional HDL. HDL has varying degrees of dysfunction reflected in impaired reverse cholesterol transport (RCT). In the context of atheroprotection, RCT occurs by 2 mechanisms: one is the well-known trans-hepatic pathway comprising macrophage free cholesterol (FC) efflux, which produces early forms of FC-rich nascent HDL (nHDL). Lecithin:cholesterol acyltransferase converts HDL-FC to HDL-cholesteryl ester while converting nHDL from a disc to a mature spherical HDL, which transfers its cholesteryl ester to the hepatic HDL receptor, scavenger receptor B1 for uptake, conversion to bile salts, or transfer to the intestine for excretion. Although widely cited, current evidence suggests that this is a minor pathway and that most HDL-FC and nHDL-FC rapidly transfer directly to the liver independent of lecithin:cholesterol acyltransferase activity. A small fraction of plasma HDL-FC enters the trans-intestinal efflux pathway comprising direct FC transfer to the intestine. SR-B1 -/- mice, which have impaired trans-hepatic FC transport, are characterized by high plasma levels of a dysfunctional FC-rich HDL that increases plasma FC bioavailability in a way that produces whole-body hypercholesterolemia and multiple pathologies. The design of future therapeutic strategies to improve RCT will have to be formulated in the context of these dual RCT mechanisms and the role of FC bioavailability. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels

NARCIS (Netherlands)

Kuivenhoven, J.A.; de Knijff, P.; Boer, J M; Smalheer, H A; Botma, G.J.; Seidell, J C; Kastelein, J.J.; Pritchard, P H

This study was designed to investigate the association(s) between heterogeneity at the cholesteryl ester transfer protein (CETP) gene locus, CETP plasma concentrations, and HDL cholesterol levels. Healthy men with the lowest, median, and highest deciles of HDL cholesterol were selected from a large

Double-Blind Randomized Placebo Controlled Trial Demonstrating Serum Cholesterol Lowering Efficacy of a Smoothie Drink with Added Plant Stanol Esters in an Indonesian Population

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Lanny Lestiani

2018-01-01

Full Text Available Indonesians have a high intake of saturated fats, a key contributing dietary factor to elevated blood cholesterol concentrations. We investigated the cholesterol lowering efficacy of a smoothie drink with 2 grams of plant stanols as esters to lower serum total and LDL-cholesterol concentrations in hypercholesterolemic Indonesian adults. The double-blind randomized placebo controlled parallel design study involved 99 subjects. Fifty subjects received control drink and dietary advice, and 49 subjects received intervention drink (Nutrive Benecol® and dietary advice. Baseline, midline (week 2, and endline (week 4 assessments were undertaken for clinical, anthropometric, and biochemical variables. Compared to control, the smoothie drink with plant stanols reduced serum LDL-cholesterol concentration by 7.6% (p<0.05 and 9.0% (p<0.05 in two and four weeks, respectively. Serum total cholesterol was reduced by 5.7% (p<0.05 compared to control in two weeks, and no further reduction was detected after four weeks (5.6%. Compared to baseline habitual diet, LDL-cholesterol was reduced by 9.3% (p<0.05 and 9.8% (p<0.05 in the plant stanol ester group in two and four weeks, respectively. We conclude that consumption of smoothie drink with added plant stanol esters effectively reduces serum total and LDL-cholesterol of hypercholesterolemic Indonesian subjects already in two weeks. Trial is registered as NCT02316808.

Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers.

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de Oliveira, Wilson Pascoalino Camargo; Tavoni, Thauany Martins; Freitas, Fatima Rodrigues; Silva, Bruna Miranda Oliveira; Maranhão, Raul Cavalcante

2017-08-01

Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1β, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.

Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus

NARCIS (Netherlands)

Dullaart, R. P. F.; de Vries, R.; Dallinga-Thie, G. M.; van Tol, A.; Sluiter, W. J.

Adipose tissue contributes to plasma levels of lipid transfer proteins and is also the major source of plasma adipokines. We hypothesized that plasma cholesteryl ester transfer protein (CETP) mass, phospholipid transfer protein (PLTP) activity and cholesteryl ester transfer (CET, a measure of CETP

Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men

NARCIS (Netherlands)

S.C. Riemens; A. van Tol (Arie); B.K. Stulp; R.P.F. Dullaart (Robin)

1999-01-01

textabstractLecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism. We evaluated the influence of insulin

Interaction of cholesterol ester transfer protein polymo- rphisms, body mass index, and birth weight with the risk of dyslipidemia in children and adolescents: the CASPIAN-III study

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Motahar Heidari-Beni

2015-11-01

Full Text Available Objective(s: This study aims to investigate joint association between cholesterol ester transfer protein (CETP polymorphisms and body mass index (BMI or birth weight with the risk of dyslipidemia in Iranian children and adolescents. Materials and Methods:This study was conducted as a sub-study of the “school-based nationwide health survey” (CASPIAN-III. We randomly selected 750 samples from the whole blood samples. Real-time PCR and high resolution melt (HRM analysis were performed to determine Taq1B (rs708272 and A373P (rs5880 polymorphisms. Results:Taq1B polymorphism increased HDL-C, and total cholesterol (TC as well as decreased triglyceride and LDL-C concentrations. LDL-C and triglyceride levels were significantly higher and HDL-C and TC levels were significantly lower among those with A373P polymorphism. CT/TT genotype in Taq1B polymorphism showed a protective effect on dyslipidemia (OR= 0.12, 95%CI: 0.07-0.20. G allele of A373P polymorphism increased the risk of dyslipidemia (OR=4.10, 95%CI: 2.14, 7.83 after adjusting the confounders. We observed interactive effects of CETP gene polymorphisms and BMI or birth weight on dyslipidemia. Conclusion:Findings showed Taq1B polymorphism might have a protective effect and A373P polymorphism had deleterious effect on dyslipidemia in Iranian children and adolescents. These associations interacted with BMI and birth weight.

Plasma Cholesteryl Ester Transfer, But Not Cholesterol Esterification, Is Related to Lipoprotein-Associated Phospholipase A(2) : Possible Contribution to an Atherogenic Lipoprotein Profile

NARCIS (Netherlands)

Dullaart, Robin P. F.; Constantinides, Alexander; Perton, Frank G.; van Leeuwen, Jeroen J. J.; van Pelt, Joost L.; de Vries, Rindert; van Tol, Arie

Context: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) 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

Sterol transfer between cyclodextrin and membranes: similar but not identical mechanism to NPC2-mediated cholesterol transfer.

Science.gov (United States)

McCauliff, Leslie A; Xu, Zhi; Storch, Judith

2011-08-30

Niemann--Pick C disease is an inherited disorder in which cholesterol and other lipids accumulate in the late endosomal/lysosomal compartment. Recently, cyclodextrins (CD) have been shown to reduce symptoms and extend lifespan in animal models of the disease. In the present studies we examined the mechanism of sterol transport by CD using in vitro model systems and fluorescence spectroscopy and NPC2-deficient fibroblasts. We demonstrate that cholesterol transport from the lysosomal cholesterol-binding protein NPC2 to CD occurs via aqueous diffusional transfer and is very slow; the rate-limiting step appears to be dissociation of cholesterol from NPC2, suggesting that specific interactions between NPC2 and CD do not occur. In contrast, the transfer rate of the fluorescent cholesterol analogue dehydroergosterol (DHE) from CD to phospholipid membranes is very rapid and is directly proportional to the acceptor membrane concentration, as is DHE transfer from membranes to CD. Moreover, CD dramatically increases the rate of sterol transfer between membranes, with rates that can approach those mediated by NPC2. The results suggest that sterol transfer from CD to membranes occurs by a collisional transfer mechanism involving direct interaction of CD with membranes, similar to that shown previously for NPC2. For CD, however, absolute rates are slower compared to NPC2 for a given concentration, and the lysosomal phospholipid lysobisphosphatidic acid (LBPA) does not stimulate rates of sterol transfer between membranes and CD. As expected from the apparent absence of interaction between CD and NPC2, the addition of CD to NPC2-deficient fibroblasts rapidly rescued the cholesterol accumulation phenotype. Thus, the recent observations of CD efficacy in mouse models of NPC disease are likely the result of CD enhancement of cholesterol transport between membranes, with rapid sterol transfer occurring during CD--membrane interactions.

Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits

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Shoucui Gao

2017-01-01

Full Text Available High levels of plasma high-density lipoprotein-cholesterol (HDL-C are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.

Optimal Use of Plant Stanol Ester in the Management of Hypercholesterolemia

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Susanna Rosin

2015-01-01

Full Text Available Plant stanol ester is a natural compound which is used as a cholesterol-lowering ingredient in functional foods and food supplements. The safety and efficacy of plant stanol ester have been confirmed in more than 70 published clinical studies and the ingredient is a well-established and widely recommended dietary measure to reduce serum cholesterol. Daily intake of 2 g plant stanols as plant stanol ester lowers LDL-cholesterol by 10%, on average. In Europe, foods with added plant stanol ester have been on the market for 20 years, and today such products are also available in many Asian and American countries. Despite the well-documented efficacy, the full potential in cholesterol reduction may not be reached if plant stanol ester is not used according to recommendations. This review therefore concentrates on the optimal use of plant stanol ester as part of dietary management of hypercholesterolemia. For optimal cholesterol lowering aiming at a lower risk of cardiovascular disease, plant stanol ester should be used daily, in sufficient amounts, with a meal and in combination with other recommended dietary changes.

Investigations on the transport and metabolism of high density lipoprotein cholesteryl esters in African green monkeys

International Nuclear Information System (INIS)

Sorci-Thomas, M.G.

1984-01-01

The metabolic fate of circulating high density lipoprotein cholesteryl esters was studied in African green monkeys to determine the significance of the lipid transfer reaction on the catabolism of lipoprotein cholesteryl esters. A method of doubly labeling both moieties of lipoprotein cholesteryl esters with [ 3 He]cholesteryl oleate and cholesteryl [ 14 C]oleate was developed for the purpose of studying plasma cholesteryl ester metabolism in vivo. In these studies the total plasma [ 3 He]cholesterol turnover resulted in production rates, which ranged from 10-17 mg/kg day, similar to previously reported values in African green monkeys and in normal lipoproteinemic humans. In contrast to the production rates calculated from the decay of plasma 3 He-radioactivity, the production rates calculated from lipoproteins labeled with cholesteryl [ 14 C]oleate were approximately 2-3 times greater. In addition to these studies, a plasma cholesteryl ester transacylation activity was demonstrated in vitro when HDL containing doubly labeled cholesteryl esters were incubated with fresh plasma. These results demonstrated that high density lipoprotein cholesteryl esters undergo transacylation in vitro, resulting in release and reesterification of free [ 3 H]cholesterol

Cholesteryl ester transfer activity in plasma measured by using solid-phase-bound high-density lipoprotein

International Nuclear Information System (INIS)

Sparks, D.L.; Frohlich, J.; Cullis, P.; Pritchard, P.H.

1987-01-01

We studied the ability of lipid-transfer factors in plasma to promote transfer, to endogenous lipoproteins, of [ 3 H]cholesteryl ester from high-density lipoprotein (HDL) covalently bound to Sepharose 4B beads. After incubation for 2 h at 37 degrees C, 12 to 14% of the [ 3 H]cholesteryl ester had been transferred to the lipoproteins of the plasma, in the proportions 57% to HDL and 43% to low- and very-low-density lipoproteins. This process was a function of the amount of plasma present and was stimulated by addition of partly purified lipid-transfer protein. Transfer also depended on the concentration of donor HDL but was independent of the amount of acceptor lipoprotein. This simple evaluation of cholesteryl ester transfer does not require removal of lipoproteins from the plasma before incubation

[3H]cholesteryl ester labeling and transfer among human and honhuman primate plasma lipoproteins

International Nuclear Information System (INIS)

Thomas, M.S.; Rudel, L.L.

1983-01-01

Aliquots of human and nonhuman primate plasma containing 5,5'-dithiobis (2-nitrobenzoic acid) were incubated at 37 0 C in tubes previously coated with trace amounts of tritium-labeled cholesteryl oleate ([ 3 H]CO). Initially, cholesteryl esters were transferred at a rapid rate into plasma after which the rate slowed. During 24 h of incubation, an average of 55% of the [ 3 H]CO transferred from the side of the tube into African green monkey plasma, 44% into human plasma and 21% into rat plasma. Greater than 98% of the radioactive ester transferred into plasma was found to be associated with plasma lipoproteins that were then rapidly separated using vertical rotor density gradient ultracentrifugation. In very low density lipoprotein (VLDL)-poor plasma after 30 min incubations, high density lipoproteins (HDL) contained most of the [ 3 H]CO while 5- to 24-h incubations resulted in increased labeling of low density proteins (LDL). In VLDL-rich plasma, it was found that in addition to the labeling of HDL, VLDL contained about 25% of the labeled cholesteryl esters after 30-min incubations and, as above, the proportion in LDL subsequently increased. Compositional analyses showed that intermediate-sized LDL (ILDL) were accumulating cholesteryl ester mass while transfer occurred. LDL labeled using this method were injected intravenously into monkeys and their removal from plasma was found to be similar to that found for LDL labeled in vivo. It was concluded that this method of plasma lipoprotein cholesteryl ester labeling, presumably a result of cholesteryl ester transfer protein activity, was efficient, resulted in lipoproteins labeled only in the cholesteryl ester moiety, and induced minimal modification of lipoprotein particles that did not alter their biological activity

Low-Fat Nondairy Minidrink Containing Plant Stanol Ester Effectively Reduces LDL Cholesterol in Subjects with Mild to Moderate Hypercholesterolemia as Part of a Western Diet

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Maarit Hallikainen

2013-01-01

Full Text Available The cholesterol-lowering efficacy of plant stanol ester (STAEST added to fat- or milk-based products is well documented. However, their efficacy when added to nondairy liquid drinks is less certain. Therefore, we have investigated the cholesterol-lowering efficacy of STAEST added to a soymilk-based minidrink in the hypercholesterolemic subjects. In a randomized, double-blind, placebo-controlled parallel study, the intervention group (n=27 consumed 2.7 g/d of plant stanols as the ester in soymilk-based minidrink (65 mL/d with the control group (n=29 receiving the same drink without added plant stanols once a day with a meal for 4 weeks. Serum total, LDL, and non-HDL cholesterol concentrations were reduced by 8.0, 11.1, and 10.2% compared with controls (P<0.05 for all. Serum plant sterol concentrations and their ratios to cholesterol declined by 12–25% from baseline in the STAEST group while the ratio of campesterol to cholesterol was increased by 10% in the controls (P<0.05 for all. Serum precursors of cholesterol remained unchanged in both groups. In conclusion, STAEST-containing soymilk-based low-fat minidrink consumed once a day with a meal lowered LDL and non-HDL cholesterol concentrations without evoking any side effects in subjects consuming normal Western diet. The clinical trial registration number is NCT01716390.

EFFECT OF ADIPOSITY ON PLASMA-LIPID TRANSFER PROTEIN ACTIVITIES - A POSSIBLE LINK BETWEEN INSULIN-RESISTANCE AND HIGH-DENSITY-LIPOPROTEIN METABOLISM

NARCIS (Netherlands)

DULLAART, RPF; SLUITER, WJ; DIKKESCHEI, LD; HOOGENBERG, K; VANTOL, A

The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of

Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma

International Nuclear Information System (INIS)

Miida, T.; Fielding, C.J.; Fielding, P.E.

1990-01-01

The transfer of [ 3 H]cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t 1/2 at 37 degree C of 51 ± 8 min and an activation energy of 18.0 kCal mol -1 . There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major α-migrating class (HDL 2b ) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL 2b to smaller αHDL (particularly HDL 3 ) driven enzymatically by the lecithin-cholesterol acyltransferase reaction. Rates of transfer among αHDL were most rapid from the largest αHDL fraction (HDL 2b ), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the αHDL pathyway, with little label in pre-βHDL. The same experiments confirmed earlier data that cell-derived cholesterol is preferentially channeled through pre-βHDL. The authors suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol

Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice.

Science.gov (United States)

Lambert, G; Sakai, N; Vaisman, B L; Neufeld, E B; Marteyn, B; Chan, C C; Paigen, B; Lupia, E; Thomas, A; Striker, L J; Blanchette-Mackie, J; Csako, G; Brady, J N; Costello, R; Striker, G E; Remaley, A T; Brewer, H B; Santamarina-Fojo, S

2001-05-04

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.

Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia.

Science.gov (United States)

Kim, Jae-Yong; Seo, Juyi; Cho, Kyung-Hyun

2011-11-01

Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had 65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of inflammatory cells in the brain and liver sections. Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic serum lipid profile with elevation of CETP activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

In vitro incorporation of radiolabeled cholesteryl esters into high and low density lipoproteins

International Nuclear Information System (INIS)

Terpstra, A.H.; Nicolosi, R.J.; Herbert, P.N.

1989-01-01

We have developed and validated a method for in vitro incorporation of radiolabeled cholesteryl esters into low density (LDL) and high density lipoproteins (HDL). Radiolabeled cholesteryl esters dissolved in absolute ethanol were mixed with LDL or HDL in the presence of lipoprotein-deficient serum (LPDS) as a source of core lipid transfer activity. The efficiency of incorporation was dependent on: (a) the core lipid transfer activity and quantity of LPDS, (b) the mass of added radiolabeled cholesteryl esters, (c) the length of incubation, and (d) the amount of acceptor lipoprotein cholesterol. The tracer incorporation was documented by repeat density gradient ultracentrifugation, agarose gel electrophoresis, and precipitation with heparin-MnCl2. The radiolabeling conditions did not affect the following properties of the lipoproteins: (1) chemical composition, (2) electrophoretic mobility on agarose gels, (3) hydrated density, (4) distribution of apoproteins on SDS gels, (5) plasma clearance rates, and (6) immunoprecipitability of HDL apoproteins A-I and A-II. Rat HDL containing radiolabeled cholesteryl esters incorporated in vitro had plasma disappearance rates identical to HDL radiolabeled in vivo

13-week oral toxicity study with stanol esters in rats

NARCIS (Netherlands)

Turnbull, D.; Whittaker, M.H.; Frankos, V.H.; Jonker, D.

1999-01-01

Plant sterols and their saturated derivatives, known as stanols, reduce serum cholesterol when consumed in amounts of approximately 2 g per day. Stanol fatty acid esters have been developed as a highly fat-soluble form that may lower cholesterol more effectively than stanols. Stanol esters occur

A chimeric peptide of intestinal trefoil factor containing cholesteryl ester transfer protein B cell epitope significantly inhibits atherosclerosis in rabbits after oral administration.

Science.gov (United States)

Qi, Gaofu; Li, Jingjing; Wang, Shengying; Xin, Shanshan; Du, Peng; Zhang, Qingye; Zhao, Xiuyun

2011-04-01

Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future. Copyright © 2010 Elsevier Inc. All rights reserved.

Effect of apolipoprotein E-free high density lipoproteins on cholesterol metabolism in cultured pig hepatocytes

International Nuclear Information System (INIS)

Bachorik, P.S.; Virgil, D.G.; Kwiterovich, P.O. Jr.

1987-01-01

We studied cholesterol synthesis from [ 14 C]acetate, cholesterol esterification from [ 14 C]oleate, and cellular cholesterol and cholesteryl ester levels after incubating cells with apoE-free high density lipoproteins (HDL) or low density lipoproteins (LDL). LDL suppressed synthesis by up to 60%, stimulated esterification by up to 280%, and increased cell cholesteryl ester content about 4-fold. Esterification increased within 2 h, but synthesis was not suppressed until after 6 h. ApoE-free HDL suppressed esterification by about 50% within 2 h. Cholesterol synthesis was changed very little within 6 h, unless esterification was maximally suppressed; synthesis was then stimulated about 4-fold. HDL lowered cellular unesterified cholesterol by 13-20% within 2 h and promoted the removal of newly synthesized cholesterol and cholesteryl esters. These changes were transient; by 24 h, both esterification and cellular unesterified cholesterol returned to control levels, and cholesteryl esters increased 2-3-fold. HDL core lipid was taken up selectively from 125 I-labeled [ 3 H]cholesteryl ester- and ether-labeled HDL. LDL core lipid uptake was proportional to LDL apoprotein uptake. The findings suggest that 1) the cells respond initially to HDL or LDL with changes in esterification, and 2) HDL mediates both the removal of free cholesterol from the cell and the delivery of HDL cholesteryl esters to the cell

Analysis of the 22-NBD-cholesterol transfer between liposome membranes and its relation to the intermembrane exchange of 25-hydroxycholesterol.

Science.gov (United States)

Ishii, Haruyuki; Shimanouchi, Toshinori; Umakoshi, Hiroshi; Walde, Peter; Kuboi, Ryoichi

2010-05-01

The transfer of 22-NBD-cholesterol (22-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol) between two liposome membranes was quantitatively analyzed by using the fluorescence resonance energy transfer (FRET) method. Liposomes labeled with both 22-NBD-cholesterol and a rhodamine-labeled phosphatidylethanolamine (Rh-DHPE) were used as donor liposomes, and the 22-NBD-cholesterol transfer from these donor liposomes to acceptor liposomes prepared from same type of phosphatidylcholine was monitored. The transfer kinetics was found to be composed of a fast and a slow phase, and all kinetic measurements could be fitted with a bi-exponential model. The results obtained indicate that the 22-NBD-cholesterol transfer kinetics between liposome membranes depends on the fluidity of the liposome used and that the curvature may affect the kinetics. Furthermore, the behavior of 22-NBD-cholesterol in lipid membrane is similar to that of the oxysterol 25-hydroxycholesterol rather than cholesterol. It is proposed that 22-NBD-cholesterol can be a useful fluorescent probe to mimic the intermembrane transfer of oxidized cholesterols like 25-hydroxycholesterol, rather than that of cholesterol itself. 2010 Elsevier B.V. All rights reserved.

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2.

Science.gov (United States)

Oninla, Vincent O; Breiden, Bernadette; Babalola, Jonathan O; Sandhoff, Konrad

2014-12-01

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Phytosterol glycosides reduce cholesterol absorption in humans.

Science.gov (United States)

Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

2009-04-01

Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

Effect of a novel insulinotropic agent, succinic acid monoethyl ester ...

Indian Academy of Sciences (India)

Madhu

index (AAI) (ratio of HDL-C to total cholesterol) were studied. ... ester; FFA, free falty acids; HDL-C, high density lipoprotein-cholesterol; LDL-C, low density lipoprotein-cholesterol; ..... and impaired catabolism of triglyceride-rich particles. The.

Studies on sterol-ester hydrolase from Fusarium oxysporum. I. Partial purification and properties.

Science.gov (United States)

Okawa, Y; Yamaguchi, T

1977-05-01

1. A search for a long chain fatty acyl sterol-ester hydrolase in microorganisms led to the isolation from soil of five strains belonging to Fusarium sp. which produced strong activity in the culture medium. 2. The cholesterol esterase from Fusarium oxysporum IGH-2 was purified about 270-fold by means of CaCl2 precipitation and Sephadex G-75 column chromatography. 3. The cholesterol esterase was activated by adekatol and Triton X-100. It was inhibited by lecithin and lysolecithin, and completely inactivated by heat treatment (60 degrees C for 30 min, at pH 7.0). 4. The optimum pH of the enzyme was found to be around 7.0. 5. Among various cholesterol esters tested, cholesterol linoleate was the most suitable substrate. 6. Cholesterol esters in serum were also hydrolyzed by this enzyme.

Human plasma lecithin-cholesterol acyltransferase

International Nuclear Information System (INIS)

Jauhiainen, M.; Stevenson, K.J.; Dolphin, P.J.

1988-01-01

Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the fatty acid at the sn-2 position of lecithin to cholesterol forming lysolecithin and cholesteryl ester. The substrates for and products of this reaction are present within the plasma lipoproteins upon which the enzyme acts to form the majority of cholesteryl ester in human plasma. The authors proposed a covalent catalytic mechanism of action for LCAT in which serine and histidine residues mediate lecithin cleavage and two cysteine residues cholesterol esterification. With the aid of sulfhydryl reactive trivalent organoarsenical compounds which are specific for vicinal thiols they have probed the geometry of the catalytic site. They conclude that the two catalytic cysteine residues of LCAT (Cys 31 and Cys 184 ) are vicinal with a calculated distance between their sulfur atoms of 3.50-3.62 A. The additional residue alkylated by teh bifunctional reagent is within the catalytic site and may represent a previously identified catalytic serine or histidine residue

Cholesterol esterification by mouse liver homogenate. Contribution to the study of ACYL-CoA: Cholesterol ACYL transferase in mammalian liver

International Nuclear Information System (INIS)

Soares, M.G.C.B.

1976-01-01

A cholesterol- esterifying enzyme from mouse liver has been partially characterized. The enzyme which showed optimum activity at pH 7,1 and required ATP and CoA, was identified as an acyl CoA: cholesterol acyl transferase (E.C.2.3.1.26). As a fuction of time the percentage of esterified cholesterol increased linearly during the first hour of incubation and continued to increase but not linearly with 4 hours, after which time no further net esterefication was observed. The relative concentration of esterified cholesterol remained constant between the fourth and twelveth hours of incubation but afterwards decreased when the incubation continued until 24 hours. The cholesterol- esterifying activity was 24,0+- 2,9 nmoles cholesterol esterified per gram tissue wet weight per minute. The mean percentages of free cholesterol esterified in and 24 hours respectively were 14,8+- 1,6 e 21,9+- 4,5. The subfractionation of labelled cholesteryl esters after one hour incubation of liver homogenate with 4-C 14 -Cholesterol showed the order of preference for the formation of the different ester classes to be monounsatured > diunsatured ≥ saturated >> polyunsaturated. The properties of the enzyme frommouse liver do not markedly differ from those of the previously recorded ACAT activity of rat liver. (Author) [pt

Two-generation reproductive toxicity study of plant stanol esters in rats

NARCIS (Netherlands)

Whittaker, M.H.; Frankos, V.H.; Wolterbeek, A.P.M.; Waalkens-Berendsen, D.H.

1999-01-01

Plant stanol esters are intended for use as an ingredient in food to reduce the absorption of cholesterol from the gastrointestinal tract. Consumption of plant stanol esters has a demonstrated diet-derived public health benefit, as shown by numerous clinical studies. Plant stanol esters are

Safety evaluation of phytosterol esters. Part 3. Two-generation reproduction study in rats with phytosterol esters - A novel functional food

NARCIS (Netherlands)

Waalkens-Berendsen, D.H.; Wolterbeek, A.P.M.; Wijnands, M.V.W.; Richold, M.; Hepburn, P.A.

1999-01-01

Phytosterol esters (PE) are intended for use as a novel food ingredient with plasma cholesterol lowering activity which works by inhibiting the absorption of cholesterol from the gut. Although PE are naturally present in the normal diet, the levels are insufficiently large to ensure lowering of

Highly sensitive and selective cholesterol biosensor based on direct electron transfer of hemoglobin.

Science.gov (United States)

Zhao, Changzhi; Wan, Li; Jiang, Li; Wang, Qin; Jiao, Kui

2008-12-01

A cholesterol biosensor based on direct electron transfer of a hemoglobin-encapsulated chitosan-modified glassy carbon electrode has been developed for highly sensitive and selective analysis of serum samples. Modified by films containing hemoglobin and cholesterol oxidase, the electrode was prepared by encapsulation of enzyme in chitosan matrix. The hydrogen peroxide produced by the catalytic oxidation of cholesterol by cholesterol oxidase was reduced electrocatalytically by immobilized hemoglobin and used to obtain a sensitive amperometric response to cholesterol. The linear response of cholesterol concentrations ranged from 1.00 x 10(-5) to 6.00 x 10(-4) mol/L, with a correlation coefficient of 0.9969 and estimated detection limit of cholesterol of 9.5 micromol/L at a signal/noise ratio of 3. The cholesterol biosensor can efficiently exclude interference by the commonly coexisting ascorbic acid, uric acid, dopamine, and epinephrine. The sensitivity to the change in the concentration of cholesterol as the slope of the calibration curve was 0.596 A/M. The relative standard deviation was under 4.0% (n=5) for the determination of real samples. The biosensor is satisfactory in the determination of human serum samples.

The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

Directory of Open Access Journals (Sweden)

Se-Jin Jeong

2017-03-01

Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

Metabolism of high density lipoproteins reconstituted with [3H]cholesteryl ester and [14C]cholesterol in the rat, with special reference to the ovary

International Nuclear Information System (INIS)

Nestler, J.E.; Bamberger, M.; Rothblat, G.H.; Strauss, J.F. III

1985-01-01

In order to study the metabolism of high density lipoprotein (HDL)-carried sterol in the rat, human HDL was reconstituted with [ 14 C]cholesterol and [ 3 H]cholesteryl ester. After iv injection into immature PMSG-human CG primed rats pretreated with 4-aminopyrazolopyrimidine and aminoglutethimide, there was time-dependent accumulation of 3 H and 14 C in various organs which reached a maximum by 15-90 min. On a milligram wet weight basis, uptake of 3 H and 14 C was greatest in the adrenals, next in ovaries, followed by the liver, with little uptake by kidneys and spleen. On an organ basis, accumulation was greatest by the liver. Coadministration of excess unlabeled HDL, but not human low density lipoprotein, reduced accumulation of radioactivity by the ovaries and adrenals by 60%, indicating a specific and saturable uptake process. Granulosa cells cultured in lipoprotein-deficient medium with reconstituted HDL formed 3 H- and 14 C-labeled 20 alpha-hydroxypregn-4-en-3-one. Over a 24-h period, utilization of both [ 14 C]cholesterol and [ 3 H]cholesteryl ester was linear, but rates of utilization of the two sterol moieties were not parallel. Lysosomotropic agents had no effect on utilization of either free or esterified cholesterol for steroidogenesis but reduced degradation of 125 I-labeled low density lipoprotein apoprotein. These findings lend further support to the concept of a distinct HDL pathway in steroidogenic cells of the rat

Competition between ergosterol and cholesterol in sterol uptake and intracellular trafficking in the yeast Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Valachovic, M.; Hronska, L.; Hapala, I.

1998-01-01

The fate of internal cholesterol was evaluated in cells grown under various conditions with respect to the amount and the nature of sterols supplemented to the cells. Steryl esters accumulate in stationary phase-yeast cells and they are rapidly hydrolyzed in cells during exponential growth or ergosterol depletion. Cholesterol and other 'unnatural' sterols are esterified more efficiently that native ergosterol and it was speculated that esterification could protect cellular membranes from accumulation of these less optimal sterols. We tested this idea by monitoring the mobility of 14 C-cholesterol between free and esterified fractions in cell supplemented with cholesterol or ergosterol. It was found that cells grown on cholesterol to the stationary phase accumulated up to 80 % of label in the steryl ester fraction. Subsequent growth in sterol-free media caused sterol-depletion of plasma membrane and induced hydrolysis of 14 C- cholesteryl esters and accumulation of the label in free membranous sterol pool.Supplementation of cells with external sterols resulted in a shift in sterol trafficking and in a new accumulation of 14 C-cholesteryl esters. This indicates that the absence of an efficient proof-reading mechanism in plasma membrane that would be able to remove preferentially cholesterol from the free sterol pool in plasma membrane to steryl esters in lipidic particles. The mobility of cholesterol molecules in non-growing cells wa negligible suggesting that active growth or membrane proliferation are required for shifts of sterol molecules between these pools. (authors)

Cholesteryl ester transfer protein (cetp) inhibition in the treatment of cancer

KAUST Repository

Kaur, Mandeep; Esau, Luke E.; Sagar, Sunii

2016-01-01

In one embodiment, the invention provides methods of treatment which use therapeutically effective amounts of Choleste ryl Ester Transfer Protein (CETP) inhibitors to treat a variety of cancers. In certain embodiments, the inhibitor is a CETP-inhibiting small molecule, CETP-inhibiting antisense oligonucleotide, CETP-inhibiting siRNA or a CETP- inhibiting antibody. Related pharmaceutical compositions, kits, diagnostics and screens are also provided.

Cholesteryl ester transfer protein (cetp) inhibition in the treatment of cancer

KAUST Repository

Kaur, Mandeep

2016-09-01

In one embodiment, the invention provides methods of treatment which use therapeutically effective amounts of Choleste ryl Ester Transfer Protein (CETP) inhibitors to treat a variety of cancers. In certain embodiments, the inhibitor is a CETP-inhibiting small molecule, CETP-inhibiting antisense oligonucleotide, CETP-inhibiting siRNA or a CETP- inhibiting antibody. Related pharmaceutical compositions, kits, diagnostics and screens are also provided.

Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

Science.gov (United States)

Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

2017-01-01

Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

High-density lipoprotein cholesterol: How High

Directory of Open Access Journals (Sweden)

G Rajagopal

2012-01-01

Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

International Nuclear Information System (INIS)

Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

1987-01-01

Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

Quinoline-3-carboxamide Derivatives as Potential Cholesteryl Ester Transfer Protein Inhibitors

Directory of Open Access Journals (Sweden)

Jing-Kang Shen

2012-05-01

Full Text Available A series of novel quinoline-3-carboxamide derivatives 10–17 and 23–27 were designed and synthesized as cholesteryl ester transfer protein (CETP inhibitors. All of them exhibited activity against CETP. Particularly, compounds 24 and 26 displayed the best activity against CETP with the same inhibitory rate of 80.1%.

Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia

International Nuclear Information System (INIS)

Kita, T.; Yokode, M.; Watanabe, Y.; Narumiya, S.; Kawai, C.

1986-01-01

Cholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. This WHHL rabbit, an animal model of human familial hypercholesterolemia, has severe hypercholesterolemia, cutaneous xanthomas, and fulminant atherosclerosis due to the deficiency of the low density lipoprotein (LDL) receptor. When incubated with mouse peritoneal macrophages, the VLDL from WHHL rabbit (WHHL-VLDL) stimulated cholesteryl [ 14 C]oleate synthesis 124-fold more than did VLDL from the normal Japanese White rabbit (control-VLDL). The enhancement in cholesteryl ester synthesis and accumulation of WHHL-VLDL was due to the presence of a high affinity binding receptor site on the macrophage cell surface that mediated the uptake and lysosomal degradation of WHHL-VLDL. Competition studies showed that the uptake and degradation of 125 I-WHHL-VLDL was inhibited by unlabeled excess WHHL-VLDL and beta-migrating VLDL (beta-VLDL), but not LDL. Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL. These results suggest that macrophages possess a high affinity receptor that recognizes the cholesterol-rich VLDL present in the plasma of the WHHL rabbit and that the receptor which mediates ingestion of WHHL-VLDL seems to be the same as that for beta-VLDL and leads to cholesteryl ester deposition within macrophages. Thus, the uptake of the cholesterol-rich VLDL from the WHHL rabbit by macrophages in vivo may play a significant role in the pathogenesis of atherosclerosis in the WHHL rabbit

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to 3 g/day plant stanols as plant stanol esters and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

fat spreads, dairy products, mayonnaise and salad dressings) lowers LDL-cholesterol by 11.4 % (95% CI: 9.8 – 13.0), that the minimum duration required to achieve the maximum effect of plant stanol esters on LDL-cholesterol lowering is two to three weeks, and that while plant stanol esters added...... to foods such as margarine-type spreads, mayonnaise, salad dressings, and dairy products such as milk, yoghurts including low-fat yoghurts, and cheese have been shown consistently to lower blood LDL-cholesterol levels, the size of the cholesterol-lowering effect of plant stanols added to other food formats...

Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects: role of CETP and triglycerides

NARCIS (Netherlands)

de Vries, Rindert; Perton, Frank G.; Dallinga-Thie, Geesje M.; van Roon, Arie M.; Wolffenbuttel, Bruce H. R.; van Tol, Arie; Dullaart, Robin P. F.

2005-01-01

We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers,

Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects : Role of CETP and triglycerides

NARCIS (Netherlands)

de Vries, R; Perton, FG; Dallinga-Thie, GM; van Roon, AM; Wolffenbuttel, BHR; van Tol, A; Dullaart, RPF

2005-01-01

We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers,

Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes : effects of apolipoproteins

NARCIS (Netherlands)

Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.; van Tol, Arie

Purpose of review Type 2 diabetes frequently coincides with dyslipidemia, characterized by elevated plasma triglycerides, low high-density lipoprotein cholesterol levels and the presence of small dense low-density lipoprotein particles. Plasma lipid transfer proteins play an essential role in

On the cholesterol transfer rates in the rat. The search for a slow component (1961); Sur les vitesses de transfert du cholesterol chez le rat. Recherche d'une composante lente (1961)

Energy Technology Data Exchange (ETDEWEB)

Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1961-07-01

The ingestion of cholesterol 4-{sup 14}C during 7, 27 and 43 weeks enables one to find that the size of the cholesterol transfer space in rats is not modified by the duration of the experiment. In male rats, the results obtained confirm on the one hand that 50 to 60 per cent of the total cholesterol of the animal is renewed by transfer, and on the other hand that 40 to 60 per cent of the cholesterol of the rat is inert as regards this process. In female rats, the size of the transfer space is 10 per cent larger than in the males, but the general conclusions are the same. (author) [French] L'ingestion de cholesterol 4-{sup 14}C durant 7, 27 et 43 semaines permet de constater que la grandeur de l'espace de transfert du cholesterol chez les rats n'est pas modifie par la duree de l'experience. Pour les rats males, les resultats, d'une part, confirment que 50 a 60 pour cent du cholesterol total de l'animal est renouvele par transfert, et d'autre part, que 40 a 50 pour cent du cholesterol du rat est inerte en regard de ce processus. Pour les rats femelles, la grandeur de l'espace de transfert est superieure de 10 pour cent a celle de l'espace de transfert des males, mais les conclusions d'ensemble restent les memes. (auteur)

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one. In vivo conversion to cholesterol upon oral administration to a nonhuman primate

International Nuclear Information System (INIS)

Schroepfer, G.J. Jr.; Pajewski, T.N.; Hylarides, M.; Kisic, A.

1987-01-01

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I), a potent inhibitor of cholesterol synthesis with marked hypocholesteremic activity, has been studied in a nonhuman primate. A mixture of [2,4- 3 H]-I and [4- 14 C]-cholesterol was administered to a male baboon in the form of a feedball. Blood was samples at 4, 8, 12, 16, and 24 hr. Detailed analyses of the plasma lipids indicated very rapid absorption of I (relative to cholesterol) and metabolism to cholesterol, cholesteryl esters, and esters of I. The labeled cholesterol was characterized by chromatographic techniques and by purification by way of its dibromide derivative. The levels of 3 H in plasma associated with I, esters of I, cholesterol, and cholesteryl esters each showed a different time course. By 24 hr after the administration of [2,4- 3 H]-I, most of the 3 H in plasma was associated with cholesterol and cholesteryl esters. The levels of total 3 H and 14 C in plasma at various times after the administration of the mixture of [2,4- 3 H]-I and [4- 14 C]-cholesterol differed markedly with 3 H showing a maximum value at 4 hr and 14 C showing a maximum value at 24 hr

Simplified procedure for the in vitro assay of the initial linear rate of the reaction of lecithin-cholesterol acyltransferase in human serum

International Nuclear Information System (INIS)

Mahadevan, V.; Soloff, L.A.

1985-01-01

A simple sensitive method for the determination of the initial rate of the reaction of lecithin-cholesterol acyltransferase by equilibrating [ 3 H]cholesterol with unesterified cholesterol of human serum is described. The resulting serum is incubated for various time periods at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a fids at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a filter paper method in which a paper strip containing the labeled cholesterol is placed in serum at 4 degrees C, thereby preventing the formation of labeled cholesterol esters by the action of the enzyme. The rate of the reaction was linear up to 30 min

Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

International Nuclear Information System (INIS)

Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

1987-01-01

We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

DEFF Research Database (Denmark)

Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra

2016-01-01

: The results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum from skin...

Effects of medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities

DEFF Research Database (Denmark)

Tholstrup, T.; Ehnholm, C.; Jauhiainen, M.

2004-01-01

Background: Dietary medium-chain fatty acids (MCFAs) are of nutritional interest because they are more easily absorbed from dietary medium-chain triacylglycerols (MCTs) than are long-chain fatty acids from, for example, vegetable oils. It has generally been claimed that MCFAs do not increase plasma...... cholesterol, although this claim is poorly documented. Objective: We compared the effects of a diet rich in either MCFAs or oleic acid on fasting blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities in healthy men. Design: In a study with a double-blind, randomized, crossover...... plasma total triacylglycerol (P = 0.0361), and higher plasma glucose (P = 0.033). Plasma HDL-cholesterol and insulin concentrations and activities of cholesterol ester transfer protein and phospholipid transfer protein did not differ significantly between the diets. Conclusions: Compared with fat high...

Effect of external mass transfer on activation energy of butyl oleate ester synthesis using a whole cell bio catalyst

International Nuclear Information System (INIS)

Shahhoseini, Sh.; Nasernejad, B.; Vahabzadeh, F.

2016-01-01

In the present research, synthesis of butyl oleate ester from oleic acid and butanol using loofa-immobilized Rhizopus oryzae as a whole cell biocatalyst (LIC) was studied in which hexane was used as the hydrophobic solvent. Decrease of mass transfer limitations as result of the interface formation between the two immiscible substrates, positively affected on the reaction progress (87% as the ester product yielded within 10 h). By applying Arrhenius equation, the activation energy of the ester synthesis was determined as Ea=18.2 kJ/mol within temperature range of 15-45°C. It was notable to test appearance of the nonlinearity in Arrhenius plot which was indicative of presence of two sections. The reaction limited region was 15-35°C; Ea=27 kJ/mol and diffusion limited region was >35°C; Ea=6.8 kJ/mol. Eventually, in this research, influence of external mass transfer on activation energy with reference to the catalytic role of the LIC in the ester synthesis was discussed.

Increased plant sterol and stanol levels in brain of Watanabe rabbits fed rapeseed oil derived plant sterol or stanol esters

DEFF Research Database (Denmark)

Fricke, Christiane B.; Schrøder, Malene; Poulsen, Morten

2007-01-01

. Cholesterol synthesis in brain, indicated by lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be affected by plant sterol or stanol ester feeding. We conclude that high dose intake of plant sterol and stanol esters in Watanabe rabbits results in elevated concentrations...... of these components not only in the periphery but also in the central nervous system....... of these components in brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for familial hypercholesterolemia. Homozygous animals received either a standard diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally fed with 2 g cholesterol/kg to the respective diet...

Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

International Nuclear Information System (INIS)

Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

1986-01-01

EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

Early effects of dietary orotic acid upon liver lipid synthesis and bile cholesterol secretion in rats

International Nuclear Information System (INIS)

Tokmakjian, S.D.; Haines, D.S.

1985-01-01

Dietary orotic acid is known to cause impaired fatty acid synthesis and increased cholesterol synthesis in rats. The authors found that the impaired fatty acid synthesis occurs during the first day of orotic acid feeding and, in studies with albumin-bound [1- 14 C]palmitic acid, an associated decrease in the rate of esterification of this fatty acid into triacylglycerol, phospholipid, and cholesteryl ester was observed. These changes may result from the known decreases in liver levels of adenine nucleotides or, as reported here, from decreased liver CoASH levels in orotic acid-fed rats. The increase in hepatic cholesterol synthesis occurred during the second day of orotic acid feeding. It was detected by increased incorporation of [1,2- 14 C]acetate into cholesterol by liver slices and by a 7-fold increase in HMG-CoA reductase activity. At the same time the biliary output of cholesterol was increased 2-fold and studies using 3 H 2 O revealed that the output of newly synthesized cholesterol in bile was increased 5-fold. The content of cholesteryl ester in hepatic microsomes decreased during orotic acid feeding but free cholesterol was unchanged. The findings are interpreted to suggest that the increased bile cholesterol secretion caused by orotic acid is a result of impaired hepatic cholesterol esterification and that the increase in HMG-CoA reductase activity is a result of diminished negative feedback due to the depleted content of cholesteryl ester in the hepatic microsomes

22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ–LXRα–ABCA1 pathway in cholesterosis of the gallbladder

International Nuclear Information System (INIS)

Wang, Jing-Min; Wang, Dong; Tan, Yu-Yan; Zhao, Gang; Ji, Zhen-Ling

2014-01-01

Highlights: • Cholesterosis is a metabolic disease characterized by excessive lipid droplets. • Lipid droplet efflux is mediated by the ABCA1 transporter. • 22(R)-hydroxycholesterol can activate LXRα and up-regulate ABCA1. • Pioglitazone up-regulates ABCA1 in a PPARγ–LXRα–ABCA1-dependent manner. • 22(R)-hydroxycholesterol and pioglitazone synergistically decrease lipid droplets. - Abstract: Cholesterosis is a disease of cholesterol metabolism characterized by the presence of excessive lipid droplets in the cytoplasm. These lipid droplets are mainly composed of cholesterol esters derived from free cholesterol. The removal of excess cholesterol from gallbladder epithelial cells (GBECs) is very important for the maintenance of intracellular cholesterol homeostasis and the preservation of gallbladder function. Several lines of evidence have indicated that the activation of either peroxisome proliferator-activated receptor gamma (PPARγ) or liver X receptor α (LXRα) relates to cholesterol efflux. While pioglitazone can regulate the activation of PPARγ, 22(R)-hydroxycholesterol can activate LXRα and is a metabolic intermediate in the biosynthesis of steroid hormones. However, the effect of 22(R)-hydroxycholesterol in combination with pioglitazone on cholesterosis of the gallbladder is unclear. GBECs were treated with pioglitazone, 22(R)-hydroxycholesterol or PPARγ siRNA followed by Western blot analysis for ATP-binding cassette transporter A1 (ABCA1), PPARγ and LXRα. Cholesterol efflux to apoA-I was determined, and Oil Red O staining was performed to monitor variations in lipid levels in treated GBECs. Our data showed that 22(R)-hydroxycholesterol can modestly up-regulate LXRα while simultaneously increasing ABCA1 by 56%. The combination of 22(R)-hydroxycholesterol and pioglitazone resulted in a 3.64-fold increase in ABCA1 expression and a high rate of cholesterol efflux. Oil Red O staining showed an obvious reduction in the lipid droplets

Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism

DEFF Research Database (Denmark)

Caesar, Robert; Nygren, Heli; Orešič, Matej

2016-01-01

The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene...... of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl...... esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota...

Phytosterol glycosides reduce cholesterol absorption in humans

Science.gov (United States)

Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

2009-01-01

Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636

Simultaneous intake of beta-glucan and plant stanol esters affects lipid metabolism in slightly hypercholesterolemic subjects.

Science.gov (United States)

Theuwissen, Elke; Mensink, Ronald P

2007-03-01

Intake of food products rich in water-soluble fiber beta-glucan and products enriched with plant stanol esters lower serum cholesterol. Combining 2 functional food ingredients into one food product may achieve additional reductions of serum cholesterol. Our objective was to investigate the effects of a simultaneous intake of beta-glucan plus plant stanol esters on lipid metabolism in mildly hypercholesterolemic volunteers. In a randomized, controlled, 3-period crossover study, 40 mildly hypercholesterolemic men and women received muesli in random order twice a day for 4 wk, which provided, in total, 5 g control fiber from wheat (control muesli), 5 g oat beta-glucan (beta-glucan muesli), or 5 g oat beta-glucan plus 1.5 g plant stanols (combination muesli). beta-Glucan muesli decreased serum LDL cholesterol by 5.0% compared with control muesli (P = 0.013). Combination muesli reduced LDL cholesterol by 9.6% compared with control muesli (P < 0.001), and by 4.4% compared with beta-glucan muesli (P = 0.036). Serum HDL cholesterol and triacylglycerol concentrations did not differ after the 3 treatments. Compared with control muesli, beta-glucan muesli increased bile acid synthesis (P = 0.043) and decreased cholesterol absorption (P = 0.011). Addition of plant stanols did not influence bile acid synthesis but decreased cholesterol absorption (P < 0.001) and raised cholesterol synthesis (P = 0.016) compared with control muesli, and the plant stanols decreased cholesterol absorption compared with beta-glucan muesli (P = 0.004). The combination muesli decreased serum concentrations of sitostanol compared with control muesli (P = 0.010). Plasma concentrations of lipid-soluble antioxidants did not differ after the 3 treatments. beta-Glucan muesli effectively lowered serum LDL cholesterol concentrations. The addition of plant stanol esters to beta-glucan-enriched muesli further lowered serum LDL cholesterol, although effects were slightly less than predicted.

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

Science.gov (United States)

Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

2012-06-01

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

Directory of Open Access Journals (Sweden)

Ellis Susanti

2009-08-01

Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

Effect of γ irradiation on the activity of lecithin-cholesterol acyltransferase in plasma of the rat

International Nuclear Information System (INIS)

Dousset, N.; Douste-Blazy, L.

1975-01-01

Plasma cholesterol and lecithin-cholesterol-acyl-transferase activity are studied in irradiated rats. Ionizing radiations cause an increase of cholesterol levels in plasma, concerning mainly ester fraction. Lecithin-cholesterol-acyltransferase activity in plasma of irradiated rats is lowered 48 hours after exposure. This decreased rate of LCAT is probably the consequence of the post-irradiation hypercholesterolemia [fr

Cholesteryl Ester Transfer Protein (CETP) genotype and cognitive function in persons aged 35 years or older

NARCIS (Netherlands)

Izaks, Gerbrand J.; van der Knaap, Aafke M.; Gansevoort, Ron T.; Navis, Gerjan; Slaets, Joris P. J.; Dullaart, Robin P. F.

Common polymorphisms of the Cholestryl Ester Transfer Protein (CETP) gene may predict lower risk of cognitive decline. We investigated the association of cognitive function with CETP genotype in a population-based cohort of 4135 persons aged 35-82 years. Cognitive function was measured with the Ruff

Bakery products enriched with phytosterol esters, alpha-tocopherol and beta-carotene decrease plasma LDL-cholesterol and maintain plasma beta-carotene concentrations in normocholesterolemic men and women.

Science.gov (United States)

Quílez, Joan; Rafecas, Magda; Brufau, Gemma; García-Lorda, Pilar; Megías, Isabel; Bulló, Mònica; Ruiz, Joan A; Salas-Salvadó, Jordi

2003-10-01

The hypocholesterolemic effects of phytosterols have not been evaluated in bakery products, and the addition of liposoluble antioxidants to the carrier has never been tested. We investigated the effects of consuming croissants and magdalenas (Spanish muffins) enriched with sterol esters, alpha-tocopherol and beta-carotene on plasma lipid and fat-soluble antioxidant concentrations in normocholesterolemic, habitual consumers of bakery products following their usual diet and lifestyle. Using a randomized, double-blind, placebo-controlled design, the control (C) group (n = 29) received two pieces daily (standard croissant and muffin) and the sterol ester (SE) group (n = 28), the same products with sterol esters added (3.2 g/d) for 8 wk. Total and LDL cholesterol (LDL-C) decreased in the SE group by 0.24 mmol/L (P bakery products are excellent carriers for phytosterols, and their consumption is associated with a decrease in total and LDL-C concentrations, with no changes in alpha-tocopherol and beta-carotene. The ability of bakery products to include sufficient quantities of beta-carotene to compensate for a potential deficiency, and the fact that their efficacy was not associated with the time of day at which they were consumed, are interesting findings.

Characterization of placental cholesterol transport

DEFF Research Database (Denmark)

Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

2008-01-01

Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

ELEVATED CHOLESTERYL ESTER TRANSFER PROTEIN-ACTIVITY IN IDDM MEN WHO SMOKE - POSSIBLE FACTOR FOR UNFAVORABLE LIPOPROTEIN PROFILE

NARCIS (Netherlands)

DULLAART, RPF; GROENER, JEM; DIKKESCHEI, BD; ERKELENS, DW; DOORENBOS, H

Objectives: To determine the effect of cigarette smoking on the activity of cholesteryl ester transfer protein (CETP) and high-density (HDL), low-density (LDL), and very-low-density (VLDL) lipoproteins in insulin-dependent diabetic (IDDM) men with microvascular complications. Research Design and

Simultaneous Quantification of Free Cholesterol, Cholesteryl Esters, and Triglycerides without Ester Hydrolysis by UHPLC Separation and In-Source Collision Induced Dissociation Coupled MS/MS

Science.gov (United States)

Gardner, Michael S.; McWilliams, Lisa G.; Jones, Jeffrey I.; Kuklenyik, Zsuzsanna; Pirkle, James L.; Barr, John R.

2017-08-01

We demonstrate the application of in-source nitrogen collision-induced dissociation (CID) that eliminates the need for ester hydrolysis before simultaneous analysis of esterified cholesterol (EC) and triglycerides (TG) along with free cholesterol (FC) from human serum, using normal phase liquid chromatography (LC) coupled to atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (MS/MS). The analysis requires only 50 μL of 1:100 dilute serum with a high-throughput, precipitation/evaporation/extraction protocol in one pot. Known representative mixtures of EC and TG species were used as calibrators with stable isotope labeled analogs as internal standards. The APCI MS source was operated with nitrogen source gas. Reproducible in-source CID was achieved with the use of optimal cone voltage (declustering potential), generating FC, EC, and TG lipid class-specific precursor fragment ions for multiple reaction monitoring (MRM). Using a representative mixture of purified FC, CE, and TG species as calibrators, the method accuracy was assessed with analysis of five inter-laboratory standardization materials, showing -10% bias for Total-C and -3% for Total-TG. Repeated duplicate analysis of a quality control pool showed intra-day and inter-day variation of 5% and 5.8% for FC, 5.2% and 8.5% for Total-C, and 4.1% and 7.7% for Total-TG. The applicability of the method was demonstrated on 32 serum samples and corresponding lipoprotein sub-fractions collected from normolipidemic, hypercholesterolemic, hypertriglyceridemic, and hyperlipidemic donors. The results show that in-source CID coupled with isotope dilution UHPLC-MS/MS is a viable high precision approach for translational research studies where samples are substantially diluted or the amounts of archived samples are limited. [Figure not available: see fulltext.

Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice

NARCIS (Netherlands)

Westerterp, M.; Hoogt, C.C. van der; Haan, W. de; Offerman, E.H.; Dallinga-Thie, G.M.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

2006-01-01

OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS -

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

Science.gov (United States)

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Effect of medicinal plants on the crystallization of cholesterol

Science.gov (United States)

Saraswathi, N. T.; Gnanam, F. D.

1997-08-01

One of the least desirable calcifications in the human body is the mineral deposition in atherosclerosis plaques. These plaques principally consist of lipids such as cholesterol, cholesteryl esters, phospholipids and triglycerides. Chemical analysis of advanced plaques have shown the presence of considerable amounts of free cholesterol identified as cholesterol monohydrate crystals. Cholesterol has been crystallized in vitro. The extracts of some of the Indian medicinal plants detailed below were used as additives to study their effect on the crystallization behaviour of cholesterol. It has been found that many of the herbs have inhibitory effect on the crystallization such as nucleation, crystal size and habit modification. The inhibitory effect of the plants are graded as Commiphora mughul > Aegle marmeleos > Cynoden dactylon > Musa paradisiaca > Polygala javana > Alphinia officinarum > Solanum trilobatum > Enicostemma lyssopifolium.

Effect of doxazosin on cholesterol synthesis in cell culture

International Nuclear Information System (INIS)

D'Eletto, R.D.; Javitt, N.B.

1989-01-01

The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent

Steryl ester synthesis, storage and hydrolysis: A contribution to sterol homeostasis.

Science.gov (United States)

Korber, Martina; Klein, Isabella; Daum, Günther

2017-12-01

Sterols are essential lipids of all eukaryotic cells, appearing either as free sterols or steryl esters. Besides other regulatory mechanisms, esterification of sterols and hydrolysis of steryl esters serve to buffer both an excess and a lack of free sterols. In this review, the esterification process, the storage of steryl esters and their mobilization will be described. Several model organisms are discussed but the focus was set on mammals and the yeast Saccharomyces cerevisiae. The contribution of imbalanced cholesterol homeostasis to several human diseases, namely Wolman disease, cholesteryl ester storage disease, atherosclerosis and Alzheimer's disease, Niemann-Pick type C and Tangier disease is described. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of cholesterol solubilised in membranes on the interfacial water structure

International Nuclear Information System (INIS)

Maitra, A.; Patanjali, P.

1987-01-01

Cholesterol solubilised in the reverse micellar system of Aerosol OT in isooctane has been found to decrease the hydrophilicity of the surfactant molecule. This has been studied in detail by water proton NMR relaxation measurements in water-Aerosol OT-isooctane with and without cholesterol. It is concluded that the intermolecular hydrogen bonding between the 3β-OH group of cholesterol and the carbonyl ester of Aerosol OT is responsible for the decrease in hydrogen bonding capacity of the latter. (author). 23 refs.; 2 figs

Enzymes involved in cholesterol homeostasis in outer vs inner cortices of the guinea pig adrenal

International Nuclear Information System (INIS)

Brody, R.I.

1988-01-01

Adrenocortical cells require cholesterol for steroid hormone synthesis. Intracellular free cholesterol levels are maintained by the actions of three key enzymes: HMG CoA reductase, a rate limiting enzyme of cholesterol biosynthesis, acyl CoA:cholesterol acyltransferase (ACAT), which esterifies cholesterol to fatty acids, and cholesterol ester hydrolase (CEH), which releases stored cholesterol by clearing the ester bond. The guinea pig adrenal cortex, which can be separated into a lipid-rich outer zone and a lipid-poor inner zone, provides a good model in which to determine whether the morphological differences in these regions correlate with functional distinctions in enzymes of cholesterol homeostasis. These studies have shown that there are great differences in these enzymes in the outer and inner zones of the guinea pig adrenal cortex. The cholesterol-rich outer zone possesses greater activities of ACAT and CEH than the inner zone, and, in untreated animals, these enzymes are nearly maximally stimulated. Both zones had substantial levels of HMG CoA reductase, as measured by enzyme assay and ELISA, and these levels increased following ACTH stimulation. However, only the outer zone incorporated 14 C-acetate into steroids and cholesterol to any great degree in vitro, and only in this zone was incorporation increased following incubation of cultures with ACTH. The discrepancies between HMG CoA reductase levels and 14 C-acetate incorporation in the inner zone indicate that cholesterol synthesis must be regulated differently in this zone

The Relationship Between Genetic Variations of the Cholesteryl Ester Transfer Protein Gene and Coronary Artery Disease in Turkish Subjects

Science.gov (United States)

Gundogdu, Fuat; Gurlertop, Yekta; Pirim, Ibrahim; Sevimli, Serdar; Dogan, Hasan; Arslan, Sakir; Aksoy, Hulya; Karakelloglu, Sule; Senocak, Huseyin

2009-01-01

Objective Although the relationship between cholesteryl ester transfer protein (CETP) and cholesterol metabolism has been characterized in recent years, the effect of CETP genetic variants associated with coronary artery disease (CAD) is still unclear. Therefore, we investigated the association between CETP gene polymorphism and levels of lipid in patients with CAD. Materials and Methods We conducted a case-control study that included 194 unrelated subjects who underwent coronary angiography for suspected ischemic heart disease. This group was divided into 96 patients with angiographically documented CAD and 98 subjects (individuals matched for age and gender) without angiographically documented CAD (CAD-free subjects), all of whom were studied to examine the genotypic distribution of the CETP gene polymorphism in CAD. Genotyping was performed via polymerase chain reaction. Results Of the 96 patients with CAD, 38 (40%) were B1B1, 42 (44%) B1B2 and 16 (16%) B2B2, compared with the control subjects, of which 35 (36%) were B1B1, 44 (45%) B1B2 and 19 (19%) B2B2. There were no significant differences between patients with CAD and control subjects in the distribution of the CETP gene polymorphism. Patients with the B1B1 genotype had lower high-density lipoprotein-cholesterol (HDL-C) and higher triglyceride (TG) levels than patients with the B2B2 genotype (p<0.05). In addition, among control subjects HDL-C levels were significantly higher in subjects with the B2B2 genotype than in subjects with the B1B1 genotype (p<0.01). Conclusion Our results suggest that genetic variations of the CTEP gene may be responsible for low HDL-C levels but may not be considered as a risk factor for CAD in the Turkish population. PMID:25610061

Association of a cholesteryl ester transfer protein variant (rs1800777) with fat mass, HDL cholesterol levels, and metabolic syndrome.

Science.gov (United States)

de Luis, Daniel; Izaola, Olatz; Primo, David; Gomez, Emilia; Lopez, Juan Jose; Ortola, Ana; Aller, Rocio

2018-04-25

There is little evidence of the association between CETP SNPs and obesity and/or related metabolic parameters. To analyze the association of the polymorphism rs1800777 of the CETP gene with anthropometric parameters, lipid profile, metabolic syndrome and its components, and adipokine levels in obese subjects without type 2 diabetes mellitus or hypertension. A population of 1005 obese subjects was analyzed. Electrical bioimpedance was performed, and blood pressure, presence of metabolic syndrome, dietary intake, physical activity, and biochemical tests were recorded. Nine hundred and sixty eight patients (96.3%) had the GG genotype, 37 patients the GA genotype (3.7%) (no AA genotype was detected). Fat mass (delta: 4.4±1.1kg; p=0.04), waist circumference (delta: 5.6±2.1cm; p=0.02), and waist to hip ratio (delta: 0.04±0.01cm; p=0.01) were higher in A allele carriers than in non-A allele carriers. HDL cholesterol levels were lower in A allele carriers than in non-A allele carriers (delta: 4.2±1.0mg/dL; p=0.04). In the logistic regression analysis, the GA genotype was associated to an increased risk of central obesity (OR 7.55, 95% CI 1.10-55.70, p=0.02) and low HDL cholesterol levels (OR 2.46, 95% CI 1.23-4.91, p=0.014). The CETP variant at position +82 is associated to lower HDL cholesterol levels, increased fat mass, and central obesity in obese subjects. These results may suggest a potential role of this variant gene in pathophysiology of adipose tissue. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

The cholesterol space of the rat; L'espace cholesterol du rat

Energy Technology Data Exchange (ETDEWEB)

Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1959-07-01

The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [French] Les experiences ont consiste a faire ingerer quotidiennement une meme masse de cholesterol radioactif a des rats, durant des laps de temps variables. L'evolution de la radioactivite specifique du carbone-14 du cholesterol des organes en fonction du temps permet d'obtenir des renseignements relatifs au transport du cholesterol dans l'organisme. 1) L'espace cholesterol defini comme l'ensemble des molecules susceptibles d'etre transferees des organes dans le serum, et vice-versa, represente au plus 50 pour cent du cholesterol total du rat adulte. 2) Le va et vient incessant entre le cholesterol tissulaire et le cholesterol serique renouvelle en totalite ou en

Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects

NARCIS (Netherlands)

Ford, John; Lawson, Matt; Fowler, David; Maruyama, Nobuko; Mito, Seiji; Tomiyasu, Koichi; Kinoshita, Shuji; Suzuki, Chisa; Kawaguchi, Atsuhiro; Round, Patrick; Boyce, Malcolm; Warrington, Steve; Weber, Werner; van Deventer, Sander; Kastelein, John J. P.

2014-01-01

Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5,

Lipid Exchange Mechanism of the Cholesteryl Ester Transfer Protein Clarified by Atomistic and Coarse-grained Simulations

DEFF Research Database (Denmark)

Koivuniemi, A.; Vuorela, T.; Kovanen, P. T.

2012-01-01

molecular dynamics simulations to unravel the mechanisms associated with the CETP-mediated lipid exchange. To this end we used both atomistic and coarse-grained models whose results were consistent with each other. We found CETP to bind to the surface of high density lipoprotein (HDL) -like lipid droplets......Cholesteryl ester transfer protein (CETP) transports cholesteryl esters, triglycerides, and phospholipids between different lipoprotein fractions in blood plasma. The inhibition of CETP has been shown to be a sound strategy to prevent and treat the development of coronary heart disease. We employed...... evidence that helix X acts as a lid which conducts lipid exchange by alternating the open and closed states. The findings have potential for the design of novel molecular agents to inhibit the activity of CETP....

Functionalization of epoxy esters with alcohols as stoichiometric reagents.

Science.gov (United States)

Pavlović, Dona; Modec, Barbara; Dolenc, Darko

2015-01-01

Glycidyl esters, frequently employed as reactive groups on polymeric supports, were functionalized with alcohols as stoichiometric reagents, yielding β-alkoxyalcohols. Among the solvents studied, best results were obtained in ethers in the presence of a strong proton acid as a catalyst. Alcohols include simple alkanols, diols, protected polyols, 3-butyn-1-ol 3-hydroxypropanenitrile and cholesterol. This protocol represents a convenient way for introduction of various functionalities onto epoxy-functionalized polymers. Under the reaction conditions, some side reactions take place, mostly due to the reactive ester group and water present in the reaction mixture.

Influence of the membrane environment on cholesterol transfer.

Science.gov (United States)

Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

2017-12-01

Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides

NARCIS (Netherlands)

Borggreve, Susanna E.; Hillege, Hans L.; Dallinga-Thie, Geesje M.; de Jong, Paul E.; Wolffenbuttel, Bruce H. R.; Grobbee, Diederik E.; van Tol, Arie; Dullaart, Robin P. F.

Aims High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. Methods and

High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides

NARCIS (Netherlands)

Borggreve, Susanna E.; Hillege, Hans L.; Dallinga-Thie, Geesje M.; de Jong, Paul E.; Wolffenbuttel, Bruce H. R.; Grobbee, Diederik E.; van Tol, Arie; Dullaart, Robin P. F.

2007-01-01

High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. A nested

Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

Science.gov (United States)

Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Moderate intake of myristic acid in sn-2 position has beneficial lipidic effects and enhances DHA of cholesteryl esters in an interventional study.

Science.gov (United States)

Dabadie, Henry; Peuchant, Evelyne; Bernard, Mireille; LeRuyet, Pascale; Mendy, François

2005-06-01

Among the saturated fatty acids (SFA), myristic acid is known to be one of the most atherogenic when consumed at high levels. Our purpose was to compare the effects of two moderate intakes of myristic acid on plasma lipids in an interventional study. Twenty-five male monks without dyslipidemia were given two isocaloric diets for 5 weeks each. In diet 1, 30% of the calories came from fat (8% SFA, 0.6% myristic acid) and provided 200 mg cholesterol/day. Calories of diet 2 were 34% fat (11% SFA, 1.2% myristic acid) with the same levels of oleate, linoleate, alpha-linolenate and cholesterol. A baseline diet was provided before each diet. In comparison with baseline, diets 1 and 2 induced a decrease in total cholesterol, LDL-cholesterol and triglycerides (Pdiet 2 than after diet 1 whereas HDL-cholesterol was higher (Pdiet 2 vs. baseline (Pdiet 1 (Pdiets were associated with an increase in alpha-linolenate of cholesteryl esters (Pdiet 2 was associated with an increase in DHA of cholesteryl esters (Pdiet 2, myristic acid intake was positively correlated with myristic acid of phospholipids, and alpha-linolenic acid intake was correlated with alpha-linolenic acid of cholesteryl esters. Moderate intake (1.2% of total calories) of myristic acid has beneficial lipidic effects and enhances DHA of cholesteryl esters.

The cholesterol space of the rat

International Nuclear Information System (INIS)

Chevallier, F.

1959-01-01

The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [fr

Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

Directory of Open Access Journals (Sweden)

Yuguang Lin

2011-01-01

Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

Science.gov (United States)

Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

1986-02-12

Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

Differential effects of gemfibrozil and fenofibrate on reverse cholesterol transport from macrophages to feces in vivo.

Science.gov (United States)

Rotllan, Noemí; Llaverías, Gemma; Julve, Josep; Jauhiainen, Matti; Calpe-Berdiel, Laura; Hernández, Cristina; Simó, Rafael; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

2011-02-01

Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARα agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [(3)H]cholesterol-labeled mouse macrophages were injected intraperitoneally into hApoA-ITg mice treated with intragastric doses of fenofibrate, gemfibrozil or a vehicle solution for 17days, and radioactivity was determined in plasma, liver and feces. Fenofibrate, but not gemfibrozil, enhanced [(3)H]cholesterol flux to plasma and feces of female hApoA-ITg mice. Fenofibrate significantly increased plasma HDLc, HDL phospholipids, hApoA-I levels and phospholipid transfer protein activity, whereas these parameters were not altered by gemfibrozil treatment. Unlike gemfibrozil, fenofibrate also induced the generation of larger HDL particles, which were more enriched in cholesteryl esters, together with higher potential to generate preβ-HDL formation and caused a significant increase in [(3)H]cholesterol efflux to plasma. Our findings demonstrate that fenofibrate promotes RCT from macrophages to feces in vivo and, thus, highlight a differential action of this fibrate on HDL. Copyright © 2010 Elsevier B.V. All rights reserved.

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

Science.gov (United States)

Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

Directory of Open Access Journals (Sweden)

Marina P Bertato

2012-01-01

Full Text Available OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in

3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

International Nuclear Information System (INIS)

Saint, C.; Gallo, I.; Kantorow, M.; Bailey, J.M.

1986-01-01

Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14 C-cholesteryl oleate with an I 50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Science.gov (United States)

Pereira, Miria G.; Nakayasu, Ernesto S.; Sant'Anna, Celso; De Cicco, Nuccia N. T.; Atella, Georgia C.; de Souza, Wanderley; Almeida, Igor C.; Cunha-e-Silva, Narcisa

2011-01-01

Background Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells. Methodology/Principal Findings Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones. Conclusions/Significance Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation. PMID:21818313

CETP does not affect triglyceride production or clearance in APOE*3-Leiden mice

NARCIS (Netherlands)

Bijland, S.; Berg, S.A.A. van den; Voshol, P.J.; Hoek, A.M. van den; Princen, H.M.G.; Havekes, L.M.; Rensen, P.C.N.; Dijk, K.W. van

2010-01-01

The cholesteryl ester transfer protein (CETP) facilitates the bidirectional transfer of cholesteryl esters and triglycerides (TG) between HDL and (V)LDL. By shifting cholesterol in plasma from HDL to (V)LDL in exchange for VLDL-TG, CETP aggravates atherosclerosis in hyperlipidemic APOE*3-Leiden

Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol diet.

Science.gov (United States)

Zidan, Y; Bouderbala, S; Djellouli, F; Lacaille-Dubois, M A; Bouchenak, M

2014-10-15

The effects of Portulaca oleracea (Po) lyophilized aqueous extract were determined on the serum high-density lipoproteins (HDL2 and HDL3) amounts and composition, as well as on lecithin: cholesterol acyltansferase (LCAT) activity. Male Wistar rats (n = 12) were fed on 1% cholesterol-enriched diet for 10 days. After this phase, hypercholesterolemic rats (HC) were divided into two groups fed the same diet supplemented or not with Portulaca oleracea (Po-HC) (0.5%) for four weeks. Serum total cholesterol (TC) and triacylglycerols (TG), and liver TG values were respectively 1.6-, 1.8-, and 1.6-fold lower in Po-HC than in HC group. Cholesterol concentrations in LDL-HDL1, HDL2, and HDL3 were respectively 1.8, 1.4-, and 2.4-fold decreased in Po-HC group. HDL2 and HDL3 amounts, which were the sum of apolipoproteins (apos), TG, cholesteryl esters (CE), unesterified cholesterol (UC), and phospholipids (PL) contents, were respectively 4.5-fold higher and 1.2-fold lower with Po treatment. Indeed, enhanced LCAT activity (1.2-fold), its cofactor-activator apo A-I (2-fold) and its reaction product HDL2-CE (2.1-fold) were observed, whereas HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were 1.2- and 2.4-fold lower. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves reverse cholesterol transport in rat fed enriched-cholesterol diet, contributing to anti-atherogenic effects. Copyright © 2014 Elsevier GmbH. All rights reserved.

Electrical and optical properties of gold nanoparticles: applications in gold nanoparticles-cholesterol oxidase integrated systems for cholesterol sensing

Energy Technology Data Exchange (ETDEWEB)

Saxena, Urmila; Goswami, Pranab, E-mail: pgoswami@iitg.ernet.in [Indian Institute of Technology Guwahati, Department of Biotechnology (India)

2012-03-15

We describe here the application of electrical and optical properties of gold nanoparticles (AuNPs) in conjunction with cholesterol oxidase (ChOx) for cholesterol estimation. The electrocatalytic property of AuNPs was studied with spectrophotometric technique using a redox dye 2,6-dichloroindophenol (DCPIP), where AuNPs found to increase the electron transfer rate between ChOx and DCPIP by {approx}1.68-fold. This study demonstrated AuNPs as efficient electron transfer mediator for ChOx based electrochemical cholesterol biosensors. Optocatalytic property of AuNPs was used in the AuNPs seed mediated enlargement system to develop an optical detection path for cholesterol. This optical method exhibited a linear detection range of 0.01-0.1 mM and a detection limit of 10 {mu}M cholesterol. The effect of AuNPs size (13-21 nm) on the catalytic properties of AuNPs was also studied. Spectrophotometric analysis of the electron transfer process between ChOx and DCPIP with different sized AuNPs showed highest electron transfer efficiency with smaller (13 nm) AuNPs. The electrochemical bioelectrode fabricated with AuNPs and ChOx gave consensus results. Contrastingly, AuNPs size did not affect its optocatalytic activity and eventually the performance of the optical method based on the growth of AuNPs. The findings of the present study offer useful insight and perspectives for fabricating highly sensitive analytical systems based on AuNPs-ChOx complexes.

Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

Energy Technology Data Exchange (ETDEWEB)

Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

2011-10-30

We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

New conception concerning the dynamical state of cholesterol in rat; Conception nouvelle concernant l'etat dynamyque du cholesterol chez le rat

Energy Technology Data Exchange (ETDEWEB)

Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1956-03-15

It presents the study of the cholesterol metabolism in rats. This thesis has been divided in three chapters. In a first part, it will discuss about the dynamic state of biological constituents in organism and in particular the dynamic state of cholesterol. This matter will be considered, firstly under its theoretical aspect and secondly under an experimental point of view with isotopic techniques. The current data on the dynamic state of cholesterol will allow to identify the essential points which are the subject of this research. In particular, the full understanding of the different cholesterol origins (diet, biosynthesis or formation of cholesterol from degradation or transformation of precursors as acetate or butyric acid for example) and the different cholesterol disappearance way (excretion, destruction, transformation or esters formation) is necessary to further research. In a second part, the experimental techniques and methods are described. A brief presentation of the methods for the study of the cholesterol transport and synthesis will be given as well as the experimental conditions and in particular the animal diet and cholesterol ingestion, the administration of acetate and {gamma}-phenyl {alpha}-aminobutyric. The different preparations of the {sup 14}C labelled cholesterol are also described as well as the extraction and measuring of the specific {sup 14}C radioactivity in the animal tissues extract, carbon dioxide gas and sodium acetate. Finally, the results will be given and discussed according to the way of intake: a radioactive cholesterol ingestion or an acetate intraperitoneal injection. (M.P.)

Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

NARCIS (Netherlands)

Diekman, M. J.; Anghelescu, N.; Endert, E.; Bakker, O.; Wiersinga, W. M.

2000-01-01

Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles

Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels

Directory of Open Access Journals (Sweden)

Hinds David A

2004-11-01

Full Text Available Abstract Association studies are used to identify genetic determinants of complex human traits of medical interest. With the large number of validated single nucleotide polymorphisms (SNPs currently available, two limiting factors in association studies are genotyping capability and costs. Pooled DNA genotyping has been proposed as an efficient means of screening SNPs for allele frequency differences in case-control studies and for prioritising them for subsequent individual genotyping analysis. Here, we apply quantitative pooled genotyping followed by individual genotyping and replication to identify associations with human serum high-density lipoprotein (HDL cholesterol levels. The DNA from individuals with low and high HDL cholesterol levels was pooled separately, each pool was amplified by polymerase chain reaction in triplicate and each amplified product was separately hybridised to a high-density oligonucleotide array. Allele frequency differences between case and control groups with low and high HDL cholesterol levels were estimated for 7,283 SNPs distributed across 71 candidate gene regions spanning a total of 17.1 megabases. A novel method was developed to take advantage of independently derived haplotype map information to improve the pooled estimates of allele frequency differences. A subset of SNPs with the largest estimated allele frequency differences between low and high HDL cholesterol groups was chosen for individual genotyping in the study population, as well as in a separate replication population. Four SNPs in a single haplotype block within the cholesteryl ester transfer protein (CETP gene interval were significantly associated with HDL cholesterol levels in both populations. Our study is among the first to demonstrate the application of pooled genotyping followed by confirmation with individual genotyping to identify genetic determinants of a complex trait.

The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

Science.gov (United States)

La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

2014-07-01

Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. © 2014

Fragment-based discovery of novel pentacyclic triterpenoid derivatives as cholesteryl ester transfer protein inhibitors.

Science.gov (United States)

Chang, Yongzhi; Zhou, Shuxi; Li, Enqin; Zhao, Wenfeng; Ji, Yanpeng; Wen, Xiaoan; Sun, Hongbin; Yuan, Haoliang

2017-01-27

Cholesteryl Ester Transfer Protein (CETP) is an important therapeutic target for the treatment of atherosclerotic cardiovascular disease. Our molecular modeling study revealed that pentacyclic triterpenoid compounds could mimic the protein-ligand interactions of the endogenous ligand cholesteryl ester (CE) by occupying its binding site. Alignment of the docking conformations of oleanolic acid (OA), ursolic acid (UA) and the crystal conformations of known CETP inhibitor Torcetrapib in the active site proposed the applicability of fragment-based drug design (FBDD) approaches in this study. Accordingly, a series of pentacyclic triterpenoid derivatives have been designed and synthesized as novel CETP inhibitors. The most potent compound 12e (IC 50 :0.28 μM) validated our strategy for molecular design. Molecular dynamics simulations illustrated that the more stable hydrogen bond interaction of the UA derivative 12e with Ser191 and stronger hydrophobic interactions with Val198, Phe463 than those of OA derivative 12b mainly led to their significantly different CETP inhibitory activity. These novel potent CETP inhibitors based on ursane-type scaffold should deserve further investigation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Total cholesterol in serum determined by isotope dilution/mass spectrometry, with liquid-chromatographic separation

International Nuclear Information System (INIS)

Takatsu, Akiko; Nishi, Sueo

1988-01-01

We describe an accurate, precise method for determination of total serum cholesterol by isotope dilution/mass spectrometry (IDMS) with liquid chromatographic separation. After adding [3,4- 13 C] cholesterol to serum and hydrolyzing the cholesterol esters, we extract the total cholesterol. High-performance liquid chromatography (HPLC) is used to separate the extracted cholesterol for measurement by electron-impact mass spectrometry with use of a direct-insertion device. To evaluate the specificity and the accuracy of this method, we also studied the conventional IDMS method, which involves converting cholesterol to the trimethylsilyl ether and assay by gas chromatography-mass spectrometry with use of a capillary column. The coefficient of variation for the HPLC method was a little larger than for the conventional method, but mean values by each method agreed within 1% for all sera tested. (author)

Preparation and evaluation of unilamellar liposomes incorporating boron-containing derivatives of cholesterol

International Nuclear Information System (INIS)

Feakes, D.A.; Tate, C.C.; Stefanutti, S.J.

2000-01-01

The application of boron neutron capture therapy is dependent on the identification and preparation of boron-containing compounds that can be delivered and retained by the tumor cells. Unilamellar liposomes have been investigated as potential tumor-specific delivery vehicles for boron-containing compounds that have no inherent tumor specificity. A series of carborane-containing derivatives of cholesterol have been prepared and incorporated into the bilayer of unilamellar liposomes. The cholesterol derivatives vary in the linker moiety (ester and ether), the chain length between the cholesterol and the carborane substituent, and the identity of the carborane group itself (closo- and nido-). The ability of the boron-containing derivatives of cholesterol to be incorporated into the bilayer of the unilamellar liposomes and the stability of the resulting liposome formulations will be presented. (author)

New conception concerning the dynamical state of cholesterol in rat; Conception nouvelle concernant l'etat dynamyque du cholesterol chez le rat

Energy Technology Data Exchange (ETDEWEB)

Chevallier, F. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1956-03-15

It presents the study of the cholesterol metabolism in rats. This thesis has been divided in three chapters. In a first part, it will discuss about the dynamic state of biological constituents in organism and in particular the dynamic state of cholesterol. This matter will be considered, firstly under its theoretical aspect and secondly under an experimental point of view with isotopic techniques. The current data on the dynamic state of cholesterol will allow to identify the essential points which are the subject of this research. In particular, the full understanding of the different cholesterol origins (diet, biosynthesis or formation of cholesterol from degradation or transformation of precursors as acetate or butyric acid for example) and the different cholesterol disappearance way (excretion, destruction, transformation or esters formation) is necessary to further research. In a second part, the experimental techniques and methods are described. A brief presentation of the methods for the study of the cholesterol transport and synthesis will be given as well as the experimental conditions and in particular the animal diet and cholesterol ingestion, the administration of acetate and {gamma}-phenyl {alpha}-aminobutyric. The different preparations of the {sup 14}C labelled cholesterol are also described as well as the extraction and measuring of the specific {sup 14}C radioactivity in the animal tissues extract, carbon dioxide gas and sodium acetate. Finally, the results will be given and discussed according to the way of intake: a radioactive cholesterol ingestion or an acetate intraperitoneal injection. (M.P.)

Sterol biosynthesis from acetate and the fate of dietary cholesterol and desmosterol in crabs

International Nuclear Information System (INIS)

Teshima, Shin-ichi; Kanazawa, Akio; Okamoto, Haruhito

1976-01-01

This paper deals with the sterol-synthesizing ability and the fate of dietary sterols, cholesterol and desmosterol, in the crabs, Sesarma dehaani and Helice tridens. Injected acetate-1- 14 C was not incorporated into either squalene or sterols in the above crabs. This suggested that the sterol-synthesizing ability from acetate is absent or weak in the crabs, S. dehaani and H. tridens. The apparent percentage absorptions of dietary cholesterol and desmosterol from the digestive tracts were 91.9 and 90.9, respectively. The ingested cholesterol and desmosterol were metabolized to steryl esters and polar compounds but only slightly to water-soluble sterols. Also, it was shown that the crab, S. dehaani, is capable of converting desmosterol to cholesterol. (auth.)

Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

Science.gov (United States)

Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

2018-01-01

Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

Directory of Open Access Journals (Sweden)

Subedi BH

2014-04-01

Full Text Available Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD is low high-density lipoprotein cholesterol (HDL-C. Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters.

Science.gov (United States)

Wilson, Thomas A; Nicolosi, Robert J; Delaney, Bryan; Chadwell, Kim; Moolchandani, Vikas; Kotyla, Timothy; Ponduru, Sridevi; Zheng, Guo-Hua; Hess, Richard; Knutson, Nathan; Curry, Leslie; Kolberg, Lore; Goulson, Melanie; Ostergren, Karen

2004-10-01

Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW.

Acrolein impairs the cholesterol transport functions of high density lipoproteins.

Science.gov (United States)

Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

2015-01-01

High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

Cholesterol metabolism in blood cells of irradiated rats

International Nuclear Information System (INIS)

Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

1985-01-01

Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro

International Nuclear Information System (INIS)

Roberts, D.C.K.; Miller, N.E.; Price, S.G.L.; Crook, D.; Cortese, C.; Ville, A. La; Masana, L.; Lewis, B.

1985-01-01

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 0 C in human serum (d > 1.215) that had been prelabelled with [4- 14 C]cholesteryl oleate or [1,2- 3 H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. .pmol -1 (46d.p.m. .ng -1 ) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction. (author)

Novel Synthesis of Phytosterol Ester from Soybean Sterol and Acetic Anhydride.

Science.gov (United States)

Yang, Fuming; Oyeyinka, Samson A; Ma, Ying

2016-07-01

Phytosterols are important bioactive compounds which have several health benefits including reduction of serum cholesterol and preventing cardiovascular diseases. The most widely used method in the synthesis of its ester analogous form is the use of catalysts and solvents. These methods have been found to present some safety and health concern. In this paper, an alternative method of synthesizing phytosterol ester from soybean sterol and acetic anhydride was investigated. Process parameters such as mole ratio, temperature and time were optimized. The structure and physicochemical properties of phytosterol acetic ester were analyzed. By the use of gas chromatography, the mole ratio of soybean sterol and acetic anhydride needed for optimum esterification rate of 99.4% was 1:1 at 135 °C for 1.5 h. FTIR spectra confirmed the formation of phytosterol ester with strong absorption peaks at 1732 and 1250 cm(-1) , which corresponds to the stretching vibration of C=O and C-O-C, respectively. These peaks could be attributed to the formation of ester links which resulted from the reaction between the hydroxyl group of soybean sterol and the carbonyl group of acetic anhydride. This paper provides a better alternative to the synthesis of phytosterol ester without catalyst and solvent residues, which may have potential application in the food, health-care food, and pharmaceutical industries. © 2016 Institute of Food Technologists®

Use of stable isotopes in the study of human cholesterol metabolism

International Nuclear Information System (INIS)

Virelizier, H.; Hagemann, R.

1979-01-01

An experimental procedure based on the use of stable isotopes spiked molecules of cholesterol, allows the measurement in faecal cholesterol of the relative parts coming from the plasma by transfer (deuterium spiked molecules), from the non absorbed alimentary cholesterol ( 13 C spiked molecules) and from the external intestinal secretion (not labelled way). The patient receive a dose of D 8 (2, 2', 3, 4, 4', 6, 7, 7') cholesterol intravenously and an oral dose of 3,4 13 C cholesterol. The plasmatic cholesterol transfer is calculated from the ratio of the measured dilutions of the faecal and plasmatic D 8 cholesterol. The non absorbed cholesterol is estimated from the percentage of 13 C cholesterol measured in the faecal sterols within the six days following the oral dose ingestion. The D 8 cholesterol dilutions are measured using the GC-MS technique on the trimethylsilyl derivatives of cholesterol. Dilutions up to 1/4000 can be measured. The 13 C enriched faecal cholesterol is converted into CO 2 and the 13 C/ 12 C ratios are measured on a dual collector mass spectrometer. Dilutions up to 1/5000 of the 3,4 13 C cholesterol can be detected. The details of the analytical procedure are given

Hepatic expression of inflammatory genes and microRNAs in pigs with high “cholesteryl ester transfer protein” (CETP) activity

DEFF Research Database (Denmark)

Cirera, Susanna; Tørsleff, Benedicte C Juul; Ritz, Christian

2016-01-01

levels (designated as CETP-high and CETP-low, respectively). Furthermore, breed and gender differences were also investigated. We found significant difference (P hepatic expression levels of several mRNAs and microRNAs between the CETP-high and -low groups (C5, IL1RN, IL18, and miR-223-5p......) promoting the redistribution of cholesteryl esters, triglycerides, and phospholipids between plasma proteins. Moreover, obesity and ORD are often linked with chronic low-grade inflammation leading to insulin resistance and endothelial and microvascular dysfunctions. The aim of this study was to detect...... differences in the hepatic expression of genes involved in low-grade inflammation and of obesity- and cholesterol-related microRNAs in two mixed breed populations of pigs (Yorkshire-Göttingen minipig, YM and Duroc-Göttingen minipig, DM) including males and females, with extreme phenotypes for CETP activity...

Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects.

Science.gov (United States)

Vinagre, J C; Vinagre, C G; Pozzi, F S; Slywitch, E; Maranhão, R C

2013-01-01

Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet. Copyright © 2011 Elsevier B.V. All rights reserved.

Changes in cholesterol content and fatty acid composition of serum lipid in irradiated rat

International Nuclear Information System (INIS)

Ohashi, Shigeru

1979-01-01

The effect of a single dose of whole body irradiation on the serum cholesterol content and fatty acid composition of serum lipids in rats was investigated. A change in the fatty acid composition of liver lipids was also observed. After 600 rad of irradiation, the cholesterol content increased, reached a maximum 3 days after irradiation, and then decreased. After irradiation, an increase in cholesterol content and a marked decrease in triglyceride content were observed, bringing about a change in the amount of total serum lipids. The fatty acid compositions of normal and irradiated rat sera were compared. The relative percentages of palmitic and oleic acids in total lipids decreased while those of stearic and arachidonic acids increased. Serum triglyceride had trace amounts of arachidonic acid and the unsaturated fatty acid component decreased after irradiation. On the other hand, unsaturated fatty acid in cholesterol ester increased after irradiation, while linoleic and arachidonic acids made up 29% and 22% in the controls and 17% and 61% after irradiation, respectively. The fatty acid composition of total liver lipids after irradiation showed a decrease in palmitic and oleic acids and an increase in stearic and arachidonic acids, the same trend as observed in serum lipid fatty acid. Liver cholesterol ester showed trace amounts of linoleic and arachidonic acids and an increase in short-chain fatty acid after irradiation. The major component of serum phospholipids was phosphatidylcholine while palmitostearyl lecithine and unsaturated fatty acid were minor components. Moreover, phosphatidylcholine and phosphatidylethanolamine were the major components of liver phospholipids, having highly unsaturated fatty acids. The changes in fatty acid composition were similar to the changes in total phospholipids. (J.P.N.)

Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

Science.gov (United States)

Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

2016-03-01

This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

Directory of Open Access Journals (Sweden)

Stephanie M Marshall

Full Text Available The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE. We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2 increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD, the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib

NARCIS (Netherlands)

Cannon, Christopher P.; Dansky, Hayes M.; Davidson, Michael; Gotto, Antonio M.; Brinton, Eliot A.; Gould, A. Lawrence; Stepanavage, Michael; Liu, Sherry Xueyu; Shah, Sukrut; Rubino, Joseph; Gibbons, Patrice; Hermanowski-Vosatka, Anne; Binkowitz, Bruce; Mitchel, Yale; Barter, Philip; Gerstman, M.; Howes, L.; Kostner, K.; Nestel, P.; Sullivan, D.; Brath, H.; Patsch, J.; Paulweber, B.; Toplak, H.; Constance, C. M.; Howlett, E.; Mymin, D.; Pliamm, L.; Saunders, K. K.; Tardif, J.-C.; Tytus, R.; Aschner, P.; Keinänen-Klukaanniemi, S.; Strandberg, T.; Taskinen, M.-R.; Luc, G.; Richter, D.; Schlienger, J. L.; Zaïr, Y.; Appel, K.-F.; Baar, M.; Luley, C.; Overhoff, U.; Pomykaj, T.; Schaefer, T.; Lau, S. T.; Lee, K. L. F.; Tan, K.; Tomlinson, B.; Tsang, M. W.; Badacsonyi, K.; Kalina, A.; Kanakaridisz, N.; Márk, L.; Péterfai, E.; Regos, L.; Reiber, I.; Takács, J.; Vértes, A.; Elis, A.; Gavish, D.; Harats, D.; Hussein, O.; Hayek, T.; Leitersdorf, E.; Ghapar, A. K. Bin Abdul; Chee, K. H.; Ismail, S. B.; Ling, K. H.; Ramanathan, G. R. L.; Sim, K. H.; Alvarado, R.; Benavides, M.; Cardona, G. E.; Gonzalez, G.; Verdejo, J.; Basart, D. C. G.; Imholz, B. P. M.; Jonker, J. J. C.; Nierop, P. R.; Posma, J. L.; Twickler, Th B.; Barrington-Ward, E.; Cutfield, R.; Friedlander, D. H.; Scott, R. S.; Istad, H.; Langslet, G.; Skjelvan, G. K.; Hoyos, S. J. Campodónico; Araniya, R. Coloma; C, A. Gallegos; Morales, C. A. Pino; Watanabe, L.; Arutyunov, G. P.; Blokhin, A. B.; Bubnova, M. G.; Marcevich, S. Y.; Sánchez, C. Alvarez; Walther, L. A. Alvarez-Sala; Extremera, B. Gil; Jimenez, F. Perez; Parreño, L. L. de Teresa; Anderberg, C.-P.; Hedin, U.; Hellberg, A.; Höök, P.; Kjellström, T.; Nilsson, P.; Olsson, A. G.; Rosenqvist, U.; Tolagen, K.; Wolff, T.; Baskin, A.; Bays, H. E.; Bernstein, R. I.; Bittar, N.; Brinton, E. A.; Chee, L. H. K.; Cottiero, R. A.; D'Agostino, R. D.; Davidson, M. H.; Denker, P. S.; Garcia, R. K.; Hippert, R. K.; Isakov, T.; Kaster, S. R.; Kerzner, B.; Klein, E. J.; Koren, M. J.; Kutner, M. E.; Liljenquist, D.; Lorch, D. G.; Lorraine, R.; Lubin, B. C.; Lunde, N. M.; Majchrzak, T. J.; McKenney, J. M.; Mukherjee, S.; Muse, D. D.; Otruba, M. S.; Pappas, J. E.; Patrick, K.; Powell, S. J.; Riffer, E.; Rink, L. D.; Rohlf, J. L.; Rosen, J. B.; Rosenbilt, P. D.; Roth, E. M.; Rubenstein, C. J.; Rubino, J.; Rudolph, L. A.; Schneider, A.; Short, W. G.; Silverfield, J. C.; Suresh, D. P.; Tarshis, G. A.; Toth, P. D.; Townsend, R. W.; Wahl, T. O.; Barter, Philip J.; Brinton, Eliot; Binkowitz, Bruce S.; Wittes, Janet; Verter, Joel; Wohlford, Neil; Granger, Christopher B.; Gersh, Bernard J.; Hasselblad, Victor; Tonkin, Andrew

2009-01-01

BACKGROUND: Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein

Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. I.Production, isolation and biological properties.

Science.gov (United States)

Tomoda, H; Tabata, N; Masuma, R; Si, S Y; Omura, S

1998-07-01

Penicillium sp. FO-5637, a soil isolate, was found to produce a series of inhibitors of cholesteryl ester transfer protein (CETP). Novel active compounds, designated erabulenols A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and HPLC. Erabulenols A and B inhibit human CETP activity with IC50 values of 47.7 and 58.2 microM in an in vitro assay system containing 200 microM BSA, respectively.

An amperometric bienzymatic cholesterol biosensor based on functionalized graphene modified electrode and its electrocatalytic activity towards total cholesterol determination.

Science.gov (United States)

Manjunatha, Revanasiddappa; Shivappa Suresh, Gurukar; Melo, Jose Savio; D'Souza, Stanislaus F; Venkatesha, Thimmappa Venkatarangaiah

2012-09-15

Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto functionalized graphene (FG) modified graphite electrode. Enzymes modified electrodes were characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). FG accelerates the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx. A well defined redox peak was observed, corresponding to the direct electron transfer of the FAD/FADH(2) of ChOx. The electron transfer coefficient (α) and electron transfer rate constant (K(s)) were calculated and their values are found to be 0.31 and 0.78 s(-1), respectively. For the free cholesterol determination, ChOx-FG/Gr electrode exhibits a sensitive response from 50 to 350 μM (R=-0.9972) with a detection limit of 5 μM. For total cholesterol determination, co-immobilization of ChEt and ChOx on modified electrode, i.e. (ChEt/ChOx)-FG/Gr electrode showed linear range from 50 to 300 μM (R=-0.9982) with a detection limit of 15 μM. Some common interferents like glucose, ascorbic acid and uric acid did not cause any interference, due to the use of a low operating potential. The FG/Gr electrode exhibits good electrocatalytic activity towards hydrogen peroxide (H(2)O(2)). A wide linear response to H(2)O(2) ranging from 0.5 to 7 mM (R=-0.9967) with a sensitivity of 443.25 μA mM(-1) cm(-2) has been obtained. Copyright © 2012 Elsevier B.V. All rights reserved.

Use of plant stanol ester margarine among persons with and without cardiovascular disease: early phases of the adoption of a functional food in Finland.

Science.gov (United States)

Simojoki, Meri; Luoto, Riitta; Uutela, Antti; Rita, Hannu; Boice, John D; McLaughlin, Joseph K; Puska, Pekka

2005-06-01

The plant stanol ester margarine Benecol is a functional food that has been shown to lower effectively serum total and LDL-cholesterol. The purpose of this post-marketing study is to characterize users of plant stanol ester margarine with and without cardiovascular disease. A cohort of plant stanol ester margarine users was established based on a compilation of 15 surveys conducted by the National Public Health Institute in Finland between 1996-2000. There were 29,772 subjects aged 35-84 years in the cohort. The users of plant stanol ester margarine were identified by the type of bread spread used. The plant stanol ester margarine was used as bread spread by 1332 (4.5%) subjects. Almost half (46%) of the users reported a history of cardiovascular disease. Persons with cardiovascular disease were more likely to use plant stanol ester margarine (8%) than persons without cardiovascular disease (3%). Users with and without cardiovascular disease seemed to share similar characteristics. In particular, they were elderly people with otherwise healthy life-styles and diet. They were less likely smokers, more likely physically active and less likely obese than nonusers. The users reported being in good or average health in general and having used cholesterol-lowering drugs. Plant stanol ester margarine seems to be used by persons for whom it was designed and in a way it was meant: as part of efforts for cardiovascular disease risk reduction.

Use of plant stanol ester margarine among persons with and without cardiovascular disease: Early phases of the adoption of a functional food in Finland

Directory of Open Access Journals (Sweden)

Boice John D

2005-06-01

Full Text Available Abstract Background The plant stanol ester margarine Benecol® is a functional food that has been shown to lower effectively serum total and LDL-cholesterol. The purpose of this post-marketing study is to characterize users of plant stanol ester margarine with and without cardiovascular disease. Methods A cohort of plant stanol ester margarine users was established based on a compilation of 15 surveys conducted by the National Public Health Institute in Finland between 1996–2000. There were 29 772 subjects aged 35–84 years in the cohort. The users of plant stanol ester margarine were identified by the type of bread spread used. Results The plant stanol ester margarine was used as bread spread by 1332 (4.5% subjects. Almost half (46% of the users reported a history of cardiovascular disease. Persons with cardiovascular disease were more likely to use plant stanol ester margarine (8% than persons without cardiovascular disease (3%. Users with and without cardiovascular disease seemed to share similar characteristics. In particular, they were elderly people with otherwise healthy life-styles and diet. They were less likely smokers, more likely physically active and less likely obese than nonusers. The users reported being in good or average health in general and having used cholesterol-lowering drugs. Conclusion Plant stanol ester margarine seems to be used by persons for whom it was designed and in a way it was meant: as part of efforts for cardiovascular disease risk reduction.

Cold labelled substrate and estimation of cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

International Nuclear Information System (INIS)

Dobiasova, M.; Schuetzova, M.

1986-01-01

A new method is described of cold labelling of blood serum, plasma and body fluids containing lecithin cholesterol acyltransferase (LCAT) and/or lipoproteins for radioassay to assess the cholesterol esterification rate. The method uses the principle of transfer, in refrigeration conditions, of 14 C-cholesterol from filter paper discs to the fluids. The preparation of the disc guarantees homogeneous labelling and high stability. The use of the labelling disc was shown to be reliable, easy and fast and suitable for accurate assessment of LCAT reaction, applicable in the widest possible enzyme concentration range. It was also, found suited for the measurement of the esterification rate of rabbit intraocular fluid which is a medium with the lowest contents of the substrate and LCAT. (L.O.)

Basal-bolus insulin therapy reduces maternal triglycerides in gestational diabetes without modifying cholesteryl ester transfer protein activity.

Science.gov (United States)

Olmos, Pablo R; Borzone, Gisella R

2017-09-01

Macrosomia in the offspring of overweight/obese mothers with glucose-controlled gestational diabetes mellitus (GDM) is due to excessive rise of maternal triglycerides (TG). We aimed to ascertain whether basal-bolus insulin therapy (BBIT), or other components of the treatment, could reduce TG in GDM. We studied the records of 131 singleton pregnancies with GDM, using stepwise multiple linear regression, Mann-Whitney, χ 2 , and Jonckheere-Terpstra tests. As maternal TG increased steadily during normal pregnancy, these were transformed as z-scores. The atherogenic index of plasma (AIP) was calculated as a measure of cholesteryl ester transfer protein activity. Multiple regression showed that only BBIT (but neither limitation of weight gain nor metformin) reduced maternal TG z-scores (P = 0.011). When the 131 pregnancies were split into two groups - without BBIT (n = 58; HbA1c = 5.3 ± 0.3%) and with BBIT (n = 73; HbA1c = 5.4 ± 0.6; P = 0.2005) - we observed that BBIT (n = 73) reduced maternal TG z-scores in a dose-related fashion (Jonckheere-Terpstra P = 0.03817). The atherogenic index of plasma remained within normal range in both groups. BBIT (but not weight gain control nor metformin) reduced maternal TG in mothers with glucose-controlled GDM. This beneficial effect of BBIT was not related to changes in the cholesteryl ester transfer protein activity. © 2017 Japan Society of Obstetrics and Gynecology.

Use of plant stanol ester margarine among persons with and without cardiovascular disease: Early phases of the adoption of a functional food in Finland

OpenAIRE

Boice John D; Rita Hannu; Uutela Antti; Luoto Riitta; Simojoki Meri; McLaughlin Joseph K; Puska Pekka

2005-01-01

Abstract Background The plant stanol ester margarine Benecol® is a functional food that has been shown to lower effectively serum total and LDL-cholesterol. The purpose of this post-marketing study is to characterize users of plant stanol ester margarine with and without cardiovascular disease. Methods A cohort of plant stanol ester margarine users was established based on a compilation of 15 surveys conducted by the National Public Health Institute in Finland between 1996–2000. There were 29...

Spontaneous insertion of GPI anchors into cholesterol-rich membrane domains

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Jing Li

2018-05-01

Full Text Available GPI-Anchored proteins (GPI-APs can be exogenously transferred onto bilayer membranes both in vivo and in vitro, while the mechanism by which this transfer process occurs is unknown. In this work, we used atomistic molecular dynamics simulations and free energy calculations to characterize the essential influence of cholesterol on insertion of the GPI anchors into plasma membranes. We demonstrate, both dynamically and energetically, that in the presence of cholesterol, the tails of GPI anchors are able to penetrate inside the core of the lipid membrane spontaneously with a three-step mechanism, while in the absence of cholesterol no spontaneous insertion was observed. We ascribe the failure of insertion to the strong thermal fluctuation of lipid molecules in cholesterol-free bilayer, which generates a repulsive force in entropic origin. In the presence of cholesterol, however, the fluctuation of lipids is strongly reduced, thus decreasing the barrier for the anchor insertion. Based on this observation, we propose a hypothesis that addition of cholesterol creates vertical creases in membranes for the insertion of acyl chains. Moreover, we find that the GPI anchor could also spontaneously inserted into the boundary between cholesterol-rich and cholesterol-depleted domains. Our results shed light on the mechanism of cholesterol-mediated interaction between membrane proteins with acyl chain and plasma membranes in living cells.

Spontaneous insertion of GPI anchors into cholesterol-rich membrane domains

Science.gov (United States)

Li, Jing; Liu, Xiuhua; Tian, Falin; Yue, Tongtao; Zhang, Xianren; Cao, Dapeng

2018-05-01

GPI-Anchored proteins (GPI-APs) can be exogenously transferred onto bilayer membranes both in vivo and in vitro, while the mechanism by which this transfer process occurs is unknown. In this work, we used atomistic molecular dynamics simulations and free energy calculations to characterize the essential influence of cholesterol on insertion of the GPI anchors into plasma membranes. We demonstrate, both dynamically and energetically, that in the presence of cholesterol, the tails of GPI anchors are able to penetrate inside the core of the lipid membrane spontaneously with a three-step mechanism, while in the absence of cholesterol no spontaneous insertion was observed. We ascribe the failure of insertion to the strong thermal fluctuation of lipid molecules in cholesterol-free bilayer, which generates a repulsive force in entropic origin. In the presence of cholesterol, however, the fluctuation of lipids is strongly reduced, thus decreasing the barrier for the anchor insertion. Based on this observation, we propose a hypothesis that addition of cholesterol creates vertical creases in membranes for the insertion of acyl chains. Moreover, we find that the GPI anchor could also spontaneously inserted into the boundary between cholesterol-rich and cholesterol-depleted domains. Our results shed light on the mechanism of cholesterol-mediated interaction between membrane proteins with acyl chain and plasma membranes in living cells.

Vertically aligned carbon nanotube probes for monitoring blood cholesterol

Science.gov (United States)

Roy, Somenath; Vedala, Harindra; Choi, Wonbong

2006-02-01

Detection of blood cholesterol is of great clinical significance. The amperometric detection technique was used for the enzymatic assay of total cholesterol. Multiwall carbon nanotubes (MWNTs), vertically aligned on a silicon platform, promote heterogeneous electron transfer between the enzyme and the working electrode. Surface modification of the MWNT with a biocompatible polymer, polyvinyl alcohol (PVA), converted the hydrophobic nanotube surface into a highly hydrophilic one, which facilitates efficient attachment of biomolecules. The fabricated working electrodes showed a linear relationship between cholesterol concentration and the output signal. The efficacy of the multiwall carbon nanotubes in promoting heterogeneous electron transfer was evident by distinct electrochemical peaks and higher signal-to-noise ratio as compared to the Au electrode with identical enzyme immobilization protocol. The selectivity of the cholesterol sensor in the presence of common interferents present in human blood, e.g. uric acid, ascorbic acid and glucose, is also reported.

The effect of BAY o 2752 on bile acid absorption and cholesterol esterification

International Nuclear Information System (INIS)

Harnett, K.M.

1988-01-01

BAY o 2752 [N,N-(1,11-undecandiyl)bis(2,3-dihydro-2-methyl-1H-indole-1-carboxamide)] has been demonstrated to inhibit intestinal cholesterol absorption in rats. Studies were carried out on male Wistar rats to determine if this drug alters intestinal bile acid absorption or cholesterol esterification by acyl CoA: cholesterol acyltransferase (ACAT) or cholesterol ester hydrolase (CEH). BAY o 2752 did not affect intestinal absorption of taurocholic acid (TC) from ileal segments perfused in vivo with a tragacanth suspension in phosphate buffer containing NaCl, TC, and 24- 14 C-TC as determined by the excretory rate of radioactivity in bile. BAY o 2752 also did not affect the uptake of TC into ileal everted sacs incubated in stirred, gassed Krebs-Ringer bicarbonate buffer with 1 mM TC, 24- 14 C-TC and 3 H-inulin. BAY o 2752 also did not bind TC; TG, in a filtrate of the above solutions remained at 92-98% of control

The effect of BAY o 2752 on bile acid absorption and cholesterol esterification

Energy Technology Data Exchange (ETDEWEB)

Harnett, K.M.

1988-01-01

BAY o 2752 (N,N-(1,11-undecandiyl)bis(2,3-dihydro-2-methyl-1H-indole-1-carboxamide)) has been demonstrated to inhibit intestinal cholesterol absorption in rats. Studies were carried out on male Wistar rats to determine if this drug alters intestinal bile acid absorption or cholesterol esterification by acyl CoA: cholesterol acyltransferase (ACAT) or cholesterol ester hydrolase (CEH). BAY o 2752 did not affect intestinal absorption of taurocholic acid (TC) from ileal segments perfused in vivo with a tragacanth suspension in phosphate buffer containing NaCl, TC, and 24-{sup 14}C-TC as determined by the excretory rate of radioactivity in bile. BAY o 2752 also did not affect the uptake of TC into ileal everted sacs incubated in stirred, gassed Krebs-Ringer bicarbonate buffer with 1 mM TC, 24-{sup 14}C-TC and {sup 3}H-inulin. BAY o 2752 also did not bind TC; TG, in a filtrate of the above solutions remained at 92-98% of control.

Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R.

Science.gov (United States)

Filippakis, Harilaos; Alesi, Nicola; Ogorek, Barbara; Nijmeh, Julie; Khabibullin, Damir; Gutierrez, Catherine; Valvezan, Alexander J; Cunningham, James; Priolo, Carmen; Henske, Elizabeth P

2017-06-13

Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL-R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and pointing toward the translational potential of these pathways for the therapy of TSC.

STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

DEFF Research Database (Denmark)

Garbarino, J.; Pan, M. H.; Chin, H. F.

2012-01-01

small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...... membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well. -Garbarino, J., M. Pan, H.F. Chin, F.W. Lund, F.R. Maxfield, and J.L. Breslow. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma...

Cholesterol-lowing effect of taurine in HepG2 cell.

Science.gov (United States)

Guo, Junxia; Gao, Ya; Cao, Xuelian; Zhang, Jing; Chen, Wen

2017-03-16

A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine. The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively. The protein expressions of CYP7A1, MEK1/2, c-Jun, p-c-Jun and HNF-4α were detected. Taurine significantly reduced cellular TC and FC in dose -and time-dependent ways, and obviously increased intracellular/medium TBA and CYP7A1 expressions. There was no change in c-Jun expression, but the protein expressions of MEK1/2 and p-c-Jun were increased at 24 h and inhibited at 48 h by 20 mM taurine while HNF4α was induced after both of the 24 h and 48 h treatment. Taurine could enhance CYP7A1 expression by inducing HNF4α and inhibiting MEK1/2 and p-c-Jun expressions to promote intracellular cholesterol metabolism.

The origin of cholesterol in chyle demonstrated by nuclear indicator methods

International Nuclear Information System (INIS)

Vyas, M.

1962-01-01

In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4- 14 C- cholesterol subcutaneously or orally, or the 1- 14 C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [fr

Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx

International Nuclear Information System (INIS)

Stender, S.; Zilversmit, D.B.

1981-01-01

The arterial influx of esterified and free cholesterol from low density lipoproteins and very low density lipoproteins in 20 hypercholesterolemic rabbits was measured simultaneously by the use of lipoproteins labeled in vivo with [ 3 H]- and [ 14 C]-cholesterol. The simultaneous arterial influx of either [ 3 H]-leucine-labeled very low density lipoproteins, low density lipoproteins, high density lipoproteins, or plasma proteins was also measured in each rabbit. The arterial influx was calculated as intimal clearance, i.e., the influx of a given fraction divided by its plasma concentration. The intimal clearance of low density lipoprotein esterified cholesterol was equal to that for the apolipoproteins of that fraction, which is compatible with an arterial influx of intact low density lipoprotein molecules. The intimal clearance of very low density apolipoprotein or cholesteryl ester was less than that for low density lipoprotein, whereas high density lipoprotein and albumin clearances exceeded low density lipoprotein clearance by 1.5- to 3-fold. The intimal clearances of plasma proteins, high density, low density, and very low density lipoproteins decreased linearly with the logarithm of the macromolecular diameter. This indicates that the arterial influx of three plasma lipoprotein fractions and of plasma proteins proceeds by similar mechanisms. Apparently the relative intimal clearances of lipoproteins are more dependent on their size relative to pores or vesicular diameters at the plasma-artery interface than on specific interactions between lipoproteins and the arterial intimal surface

Cholesterol pathways affected by small molecules that decrease sterol levels in Niemann-Pick type C mutant cells.

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Madalina Rujoi

2010-09-01

Full Text Available Niemann-Pick type C (NPC disease is a genetically inherited multi-lipid storage disorder with impaired efflux of cholesterol from lysosomal storage organelles.The effect of screen-selected cholesterol lowering compounds on the major sterol pathways was studied in CT60 mutant CHO cells lacking NPC1 protein. Each of the selected chemicals decreases cholesterol in the lysosomal storage organelles of NPC1 mutant cells through one or more of the following mechanisms: increased cholesterol efflux from the cell, decreased uptake of low-density lipoproteins, and/or increased levels of cholesteryl esters. Several chemicals promote efflux of cholesterol to extracellular acceptors in both non-NPC and NPC1 mutant cells. The uptake of low-density lipoprotein-derived cholesterol is inhibited by some of the studied compounds.Results herein provide the information for prioritized further studies in identifying molecular targets of the chemicals. This approach proved successful in the identification of seven chemicals as novel inhibitors of lysosomal acid lipase (Rosenbaum et al, Biochim. Biophys. Acta. 2009, 1791:1155-1165.

Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

Directory of Open Access Journals (Sweden)

Josefin Skogsberg

2008-03-01

Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

Science.gov (United States)

Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

1997-06-01

Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

Cholesterol-based cationic lipids for gene delivery: contribution of molecular structure factors to physico-chemical and biological properties.

Science.gov (United States)

Sheng, Ruilong; Luo, Ting; Li, Hui; Sun, Jingjing; Wang, Zhao; Cao, Amin

2014-04-01

In this work, we prepared a series of cholesterol-based cationic (Cho-cat) lipids bearing cholesterol hydrophobe, natural amino acid headgroups (lysine/histidine) and linkage (carbonate ester/ether) bonds. In which, the natural amino acid headgroups made dominant contribution to their physico-chemical and biological properties. Among the lipids, the l-lysine headgroup bearing lipids (Cho-es/et-Lys) showed higher pDNA binding affinity and were able to form larger sized and higher surface charged lipoplexes than that of l-histidine headgroup bearing lipids (Cho-es/et-His), they also demonstrated higher transfection efficacy and higher membrane disruption capacities than that of their l-histidine headgroup bearing counterparts. However, compared to the contributions of the headgroups, the (carbonate ester/ether) linkage bonds showed much less affects. Besides, it could be noted that, Cho-es/et-Lys lipids exhibited very high luciferase gene transfection efficiency that almost reached the transfection level of "gold standard" bPEI-25k, made them potential transfection reagents for practical application. Moreover, the results facilitated the understanding for the structure-activity relationship of the cholesterol-based cationic lipids, and also paved a simple and efficient way for achieving high transfection efficiency by modification of suitable headgroups on lipid gene carriers. Copyright © 2014 Elsevier B.V. All rights reserved.

The dynamin chemical inhibitor dynasore impairs cholesterol trafficking and sterol-sensitive genes transcription in human HeLa cells and macrophages.

Directory of Open Access Journals (Sweden)

Emmanuelle Girard

Full Text Available Intracellular transport of cholesterol contributes to the regulation of cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In this study, we characterized the impact of dynasore, a recently described drug that specifically inhibits the enzymatic activity of dynamin, a GTPase regulating receptor endocytosis and cholesterol trafficking. Dynasore strongly inhibited the uptake of low-density lipoprotein (LDL in HeLa cells, and to a lower extent in human macrophages. In both cell types, dynasore treatment led to the abnormal accumulation of LDL and free cholesterol (FC within the endolysosomal network. The measure of cholesterol esters (CE further showed that the delivery of regulatory cholesterol to the endoplasmic reticulum (ER was deficient. This resulted in the inhibition of the transcriptional control of the three major sterol-sensitive genes, sterol-regulatory element binding protein 2 (SREBP-2, 3-hydroxy-3-methyl-coenzymeA reductase (HMGCoAR, and low-density lipoprotein receptor (LDLR. The sequestration of cholesterol in the endolysosomal compartment impaired both the active and passive cholesterol efflux in HMDM. Our data further illustrate the importance of membrane trafficking in cholesterol homeostasis and validate dynasore as a new pharmacological tool to study the intracellular transport of cholesterol.

β-CD-dextran polymer for efficient sequestration of cholesterol from phospholipid bilayers: Mechanistic and safe-toxicity investigations.

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Stelzl, Dominik; Nielsen, Thorbjørn Terndrup; Hansen, Terkel; di Cagno, Massimiliano

2015-12-30

The aim of this work was to investigate the suitability of β-cyclodextrin-dextran (BCD-dextran) polymer as cholesterol sequestering agent in vitro. For this purpose, BCD-dextran-cholesterol complexation was studied by phase solubility studies as well as with a specifically designed in vitro model based on giant unilamellar vesicles (GUVs) to evaluate the ability of this polymer to sequestrate cholesterol from phospholipid bilayers. Cholesterol-sequestering ability of BCD-dextran was also investigated on different cell lines relevant for the hematopoietic system and results were correlated to cells toxicity. BCD-dextran polymer was capable of extracting significant amount of cholesterol from phospholipid bilayers and to a higher extent in comparison to available β-cyclodextrins (BCDs). The ability of BCD-dextran in sequestering cholesterol resulted also very high on cell lines relevant for the hematopoietic system. Moreover, BCD-dextran resulted less toxic on cell cultures due to higher selectivity in sequestering cholesterol in comparison to MBCD (that sequestrated also significant amounts of cholesteryl esters). In conclusion, BCD-dextran resulted an extremely efficient cholesterol-sequestering agent and BCD-dextran resulted more selective to cholesterol extraction in comparison to other BCDs (therefore of lower cytotoxicity). This phenomenon might play a key role to develop an efficient treatment for hypercholesterolemia based on cholesterol segregation. Copyright © 2015 Elsevier B.V. All rights reserved.

Plant Sterols: Chemical and Enzymatic Structural Modifications and Effects on Their Cholesterol-Lowering Activity.

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He, Wen-Sen; Zhu, Hanyue; Chen, Zhen-Yu

2018-03-28

Plant sterols have attracted increasing attention due to their excellent cholesterol-lowering activity. However, free plant sterols have some characteristics of low oil solubility, water insolubility, high melting point, and low bioavailability, which greatly limit their application in foods. Numerous studies have been undertaken to modify their chemical structures to improve their chemical and physical properties in meeting the needs of various applications. The present review is to summarize the literature and update the progress on structural modifications of plant sterols in the following aspects: (i) synthesis of plant sterol esters by esterification and transesterification with hydrophobic fatty acids and triacylglycerols to improve their oil solubility, (ii) synthesis of plant sterol derivatives by coupling with various hydrophilic moieties to enhance their water solubility, and (iii) mechanisms by which plant sterols reduce plasma cholesterol and the effect of structural modifications on plasma cholesterol-lowering activity of plant sterols.

LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

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Anna P Lillis

Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

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Garbarino, Jeanne; Pan, Meihui; Chin, Harvey F; Lund, Frederik W; Maxfield, Frederick R; Breslow, Jan L

2012-12-01

STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the nonvesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.

Cholesterol photo-oxidation: A chemical reaction network for kinetic modeling.

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Barnaba, Carlo; Rodríguez-Estrada, Maria Teresa; Lercker, Giovanni; García, Hugo Sergio; Medina-Meza, Ilce Gabriela

2016-12-01

In this work we studied the effect of polyunsaturated fatty acids (PUFAs) methyl esters on cholesterol photo-induced oxidation. The oxidative routes were modeled with a chemical reaction network (CRN), which represents the first application of CRN to the oxidative degradation of a food-related lipid matrix. Docosahexaenoic acid (DHA, T-I), eicosapentaenoic acid (EPA, T-II) and a mixture of both (T-III) were added to cholesterol using hematoporphyrin as sensitizer, and were exposed to a fluorescent lamp for 48h. High amounts of Type I cholesterol oxidation products (COPs) were recovered (epimers 7α- and 7β-OH, 7-keto and 25-OH), as well as 5β,6β-epoxy. Fitting the experimental data with the CRN allowed characterizing the associated kinetics. DHA and EPA exerted different effects on the oxidative process. DHA showed a protective effect to 7-hydroxy derivatives, whereas EPA enhanced side-chain oxidation and 7β-OH kinetic rates. The mixture of PUFAs increased the kinetic rates several fold, particularly for 25-OH. With respect to the control, the formation of β-epoxy was reduced, suggesting potential inhibition in the presence of PUFAs. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of 3H-colesterol and its kinetics to assess the dynamics of the cholesterol metabolism in human lipoprotein fractions

International Nuclear Information System (INIS)

Grossmann, K.D.; Marek, H.; Fieber, R.S.

1982-01-01

The assessment of the dynamics of 3 H cholesterols in very low, low and high density lipoproteins, resp. lipoproteins after oral administration in normal subjects and in patients with hyperlipoproteinemia type II a and II b is described. Specific activity-time-curves of the lipoprotein fractions isolated by means of discontinuous ultracentrifugation were recorded. In order to optimize the centrifugation activity-electrophoresis-profiles of the separating steps were recorded. The fractions obtained were characterized by the determination of cholesterol, agarose electrophoresis and radioactivity measurement. The turnover of the tracer in the lipoproteins was determined on the basis of the maximum values of the specific activity-time-curves. Hyperlipoproteinemia patients showed time shifts of the maximum values especially with regard to esterized cholesterols and high density lipoprotein cholesterol as compared to healthy persons. (author)

Studies on a microbially derived, high molecular weight inhibitor of plasma cholesteryl ester transfer protein

International Nuclear Information System (INIS)

Marschke, C.K.; McGee, J.E.; Melchior, G.W.; Castle, C.K.

1989-01-01

The authors have isolated an organism which accumulates an inhibitor of Cholesteryl Ester Transfer Protein (CETP). Purification of 100,000-fold was achieved by ammonium sulfate precipitation followed by Hydroxyl Apatite, Agarose AO.5, and Mono Q (Pharmacia) chromatographies. The use of 14 C-labelled protein molecular weight standards followed by SDS-PAGE revealed some proteolytic activity. However, inhibition of the proteases did not affect the inhibitor potency. The inhibitor has an estimated molecular weight of 40 Kd and appears to exist as two forms. One form was eluted from a Mono Q column by 100 mM NaCl while the other was not bound. Our evidence indicated that the bound form was progressively denatured, or proteolyzed, during storage of the fermentation beer, to the unbound form. Importantly though this molecular change did not affect either inhibitory activity or the apparent molecular weight

Chemical constituents from bark of Cenostigma macrophyllum: cholesterol occurrence

International Nuclear Information System (INIS)

Silva, Hilris Rocha e; Silva, Carmem Cicera Maria da; Caland Neto, Laurentino Batista; Lopes, Jose Arimateia Dantas; Cito, Antonia Maria das Gracas Lopes; Chaves, Mariana H.

2007-01-01

Phytochemical investigation of the bark of Cenostigma macrophyllum (Leguminosae-Caesapinioideae) resulted in the isolation and identification of valoneic acid dilactone, ellagic acid, lupeol, alkyl ferulate, four free sterols (cholesterol, campesterol, stigmasterol and sitosterol), a mixture of sitosteryl ester derivatives of fatty acids, sitosterol-3-O-beta-D-glucopyranoside, stigmasterol-3-O-beta-D-glucopyranoside and saturated and unsaturated fatty acids. The structures of the isolated compounds were identified by 1 H and 13 C NMR spectral analysis and comparison with literature data. The mixtures of 3-beta-hydroxysterols and fatty acids were analysed by GC/MS. (author)

Effects of apolipoproteins on the kinetics of cholesterol exchange

International Nuclear Information System (INIS)

Letizia, J.Y.; Phillips, M.C.

1991-01-01

The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein

International Nuclear Information System (INIS)

Castro, G.R.; Fielding, C.J.

1988-01-01

Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with [ 3 H]cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma

Assessment of dietary exposure to flavouring substances via consumption of flavoured teas. Part II: transfer rates of linalool and linalyl esters into Earl Grey tea infusions.

Science.gov (United States)

Orth, Anne-Marie; Poplacean, Iulia; Fastowski, Oxana; Engel, Karl-Heinz

2014-01-01

The assessment of dietary exposure via the consumption of flavoured foods is a key element of the safety evaluation of flavouring substances. Linalyl acetate and linalool are the major flavouring substances in Earl Grey teas; the objective of this study was to determine their transfer rates from the tea leaves into the tea beverage upon preparation of a hot water infusion. Spiking experiments revealed a transfer rate of 66% for linalool. In contrast, the transfer rate for linalyl acetate was only 1.9%; in turn, the hydrolysis product linalool (17.0%) and a spectrum (19.9%) of degradation and rearrangement products (monoterpene alcohols, esters and hydrocarbons) were present in the tea beverage. The transfer rates were shown to be proportional to the length of the infusion. The impact of the hot water treatment on the enantiomeric compositions of linalyl acetate and linalool was determined, and structure-dependent experiments were performed by variation of the acyl and the alcohol moiety of the monoterpene ester. Comparative dietary exposure assessments demonstrated the need to take correction factors based on the experimentally determined transfer rates into account. Based on tea consumption data from the UK National Diet and Nutrition Survey (2000/2001), the exposure to linalyl acetate ranges from 0.2 mg day(-1) (average) to 1.8 mg day(-1) (high). The corresponding values for linalool are 4.2 mg day(-1) (average) and 46.6 mg day(-1) (high). The exposure of linalool via consumption of the tea beverage is approximately 26 times higher than that of linalyl acetate, although in the flavoured tea leaves the median content of linalyl acetate is approximately 1.8 times higher than that of linalool.

Study of protein-probe complexation equilibria and protein-surfactant interaction using charge transfer fluorescence probe methyl ester of N,N-dimethylamino naphthyl acrylic acid

Energy Technology Data Exchange (ETDEWEB)

Mahanta, Subrata; Balia Singh, Rupashree; Bagchi, Arnab [Department of Chemistry University of Calcutta 92, A.P.C. Road, Kolkata 700009 (India); Nath, Debnarayan [Department of Physical Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032 (India); Guchhait, Nikhil, E-mail: nguchhait@yahoo.co [Department of Chemistry University of Calcutta 92, A.P.C. Road, Kolkata 700009 (India)

2010-06-15

In this paper, we demonstrate the interaction between intramolecular charge transfer (ICT) probe-Methyl ester of N,N-dimethylamino naphthyl acrylic acid (MDMANA) with bovine serum albumin (BSA) using absorption and fluorescence emission spectroscopy. The nature of probe protein binding interaction, fluorescence resonance energy transfer from protein to probe and time resolved fluorescence decay measurement predict that the probe molecule binds strongly to the hydrophobic cavity of the protein. Furthermore, the interaction of the anionic surfactant sodium dodecyl sulphate (SDS) with water soluble protein BSA has been investigated using MDMANA as fluorescenece probe. The changes in the spectral characteristics of charge transfer fluorescence probe MDMANA in BSA-SDS environment reflects well the nature of the protein-surfactant binding interaction such as specific binding, non-cooperative binding, cooperative binding and saturation binding.

The origin of cholesterol in chyle demonstrated by nuclear indicator methods; Origines du cholesterol du chyle mises en evidence par la methode des indicateurs nucleaires

Energy Technology Data Exchange (ETDEWEB)

Vyas, M

1962-07-01

In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-{sup 14}C- cholesterol subcutaneously or orally, or the 1-{sup 14}C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [French] Pour obtenir des renseignements concernant le mecanisme de l'absorption intestinale du cholesterol, on utilise des rats porteurs d'une fistule lymphatique abdominale. Les animaux recoivent soit du cholesterol 4-{sup 14}C par voie sous-cutanee ou par voie orale, soit de l'acetate 1-{sup 14}C. L'etude des radioactivites specifiques du cholesterol du chyle, du serum, de la paroi et du contenu intestinal permet de preciser les roles joues par le cholesterol de transfert d'origine serique, par le cholesterol de synthese intestinale et par le cholesterol d'absorption, dans la formation de la lymphe et des chylomicrons. Une theorie nouvelle concernant le mecanisme de l'absorption du cholesterol est proposee. (auteur)

Stereochemical and positional specificity of the lipase/acyltransferase produced by Aeromonas hydrophila.

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Robertson, D L; Hilton, S; Buckley, J T

1992-06-02

Aeromonas species secrete a glycerophospholipid-cholesterol acyltransferase (GCAT) which shares many properties with mammalian plasma lecithin-cholesterol acetyltransferase (LCAT). We have studied the stereochemical and positional specificity of GCAT against a variety of lipid substrates using NMR spectroscopy as well as other assay methods. The results show that both the primary and secondary acyl ester bonds of L-phosphatidylcholine can be hydrolyzed but only the sn-2 fatty acid can be transferred to cholesterol. The enzyme has an absolute requirement for the L configuration at the sn-2 position of phosphatidylcholine. The secondary ester bond of D-phosphatidylcholine cannot be hydrolyzed, and this lipid is not a substrate for acyl transfer. In contrast to the phospholipases, but similar to LCAT, the enzyme does not interact stereochemically with the phosphorus of phosphatidylcholine. In fact, the phosphorus is not required for enzyme activity, as GCAT will also hydrolyze monolayers of diglyceride, although at much lower rates.

Rapid quantification of free cholesterol in tears using direct insertion/electron ionization-mass spectrometry.

Science.gov (United States)

Wei, Xiaojia Eric; Korth, John; Brown, Simon H J; Mitchell, Todd W; Truscott, Roger J W; Blanksby, Stephen J; Willcox, Mark D P; Zhao, Zhenjun

2013-12-09

To establish a simple and rapid analytical method, based on direct insertion/electron ionization-mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted. Screening, full-scan (m/z 40-600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those derived from free cholesterol, with no contribution from cholesterol esters. DI/EI-MS data acquired using selected ion monitoring (SIM) were analyzed for the abundance ratios of diagnostic ions with their stable isotope-labeled analogues arising from the D6-cholesterol internal standard. Standard curves of good linearity were produced and an on-probe limit of detection of 3 ng (at 3:1 signal to noise) and limit of quantification of 8 ng (at 10:1 signal to noise). The concentration of free cholesterol in human tears was 15 ± 6 μg/g, which was higher than in rabbit tears (10 ± 5 μg/g). A stable-isotope dilution DI/EI-SIM method for free cholesterol quantification without prior chromatographic separation was established. Using this method demonstrated that humans have higher free cholesterol levels in their tears than rabbits. This is in agreement with previous reports. This paper provides a rapid and reliable method to measure free cholesterol in small-volume clinical samples.

Amperometric cholesterol biosensor based on the direct electrochemistry of cholesterol oxidase and catalase on a graphene/ionic liquid-modified glassy carbon electrode.

Science.gov (United States)

Gholivand, Mohammad Bagher; Khodadadian, Mehdi

2014-03-15

Cholesterol oxidase (ChOx) and catalase (CAT) were co-immobilized on a graphene/ionic liquid-modified glassy carbon electrode (GR-IL/GCE) to develop a highly sensitive amperometric cholesterol biosensor. The H2O2 generated during the enzymatic reaction of ChOx with cholesterol could be reduced electrocatalytically by immobilized CAT to obtain a sensitive amperometric response to cholesterol. The direct electron transfer between enzymes and electrode surface was investigated by cyclic voltammetry. Both enzymes showed well-defined redox peaks with quasi-reversible behaviors. An excellent sensitivity of 4.163 mA mM(-1)cm(-2), a response time less than 6s, and a linear range of 0.25-215 μM (R(2)>0.99) have been observed for cholesterol determination using the proposed biosensor. The apparent Michaelis-Menten constant (KM(app)) was calculated to be 2.32 mM. The bienzymatic cholesterol biosensor showed good reproducibility (RSDsascorbic acid and uric acid. The CAT/ChOx/GR-IL/GCE showed excellent analytical performance for the determination of free cholesterol in human serum samples. © 2013 Elsevier B.V. All rights reserved.

Conversion of Exogenous Cholesterol into Glycoalkaloids in Potato Shoots, Using Two Methods for Sterol Solubilisation

Science.gov (United States)

Petersson, Erik V.; Nahar, Nurun; Dahlin, Paul; Broberg, Anders; Tröger, Rikard; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

2013-01-01

Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D) in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled), and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine) were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato. PMID:24349406

Wax Ester Analysis of Bats Suffering from White Nose Syndrome in Europe.

Science.gov (United States)

Řezanka, Tomáš; Viden, Ivan; Nováková, Alena; Bandouchová, Hana; Sigler, Karel

2015-07-01

The composition of wax esters (WE) in the fur of adult greater mouse-eared bats (Myotis myotis), either healthy or suffering from white nose syndrome (WNS) caused by the psychrophilic fungus Pseudogymnoascus destructans, was investigated by high-resolution mass spectrometry analysis in the positive ion mode. Profiling of lipid classes showed that WE are the most abundant lipid class, followed by cholesterol esters, and other lipid classes, e.g., triacylglycerols and phospholipids. WE abundance in non-polar lipids was gender-related, being higher in males than in females; in individuals suffering from WNS, both male and female, it was higher than in healthy counterparts. WE were dominated by species containing 18:1 fatty acids. Fatty alcohols were fully saturated, dominated by species containing 24, 25, or 26 carbon atoms. Two WE species, 18:1/18:0 and 18:1/20:0, were more abundant in healthy bats than in infected ones.

Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

International Nuclear Information System (INIS)

DeForge, L.E.

1989-01-01

Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate 125 I-cholesteryl iopanoate ( 125 I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of 125 I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific 125 I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guinea pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating 125 I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized 125 I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs 125 I-CI cholesteryl m-iodobenzyl ether [ 125 I-CIDE] and 125 I-cholesteryl 12-(miodophenyl)dodecyl ether [ 125 I-CIDE] into LDL

Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis.

Science.gov (United States)

He, Hongliang; Lancina, Michael G; Wang, Jing; Korzun, William J; Yang, Hu; Ghosh, Shobha

2017-06-01

Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given the central role of hepatic cholesteryl ester hydrolase (CEH) in the intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol (FC), in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer generation 5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show the increased specific uptake of Gal-G5/CEH expression vector complexes (simply Gal-G5/CEH) by hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced the intracellular hydrolysis of high density lipoprotein-associated CE (HDL-CE) and subsequent conversion/secretion of hydrolyzed FC as bile acids (BA). The increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and BA. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was also not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for the alleviation of atherosclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

Science.gov (United States)

Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

2012-05-30

Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

Synthesis of 2-(6-Acetamidobenzothiazolethioacetic Acid Esters as Photosynthesis Inhibitors

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Dusan Loos

1998-04-01

Full Text Available The synthesis and photosynthesis-inhibiting activity of 13 new 2-(6-acetamidobenzothiazolethioacetic acid esters are reported. The new compounds were prepared by acetylation of 2-(alkoxycarbonylmethylthio-6-aminobenzothiazoles with acetic anhydride. The structure of the compounds was verified by 1H NMR spectra. The compounds inhibit photosynthetic electron transfer in spinach chloroplasts. The structure - activity relation was studied. Lipophilicity was found to influence substantially photosynthetic electron transfer.

Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients

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Cal Roi

2012-08-01

Full Text Available Abstract Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT were included. Low density lipoprotein receptor-related protein 1 (LRP1, very low density lipoprotein receptor (VLDLR and low density lipoprotein receptor (LDLR expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE, triglyceride (TG and free cholesterol (FC content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy.

Synthesis and Analysis of Methacryloyl-L-Alanine Methyl Ester using fourier Transform Nuclear Magnetic Resonance

International Nuclear Information System (INIS)

Tri Darwinto

2008-01-01

Methacryloyl-L-alanine methyl ester was synthesized by reacting methacrylic acid with L-alanine methyl ester hydrochloride in triethylamine at temperature of 90 o C. Hydrogel polymer of poly(methacryloyl-L-alanine methyl ester) was much used for diagnosis and therapy of vascular tumor. The molecular structure methacryloyl-L-alanine methyl ester analyzed by fourier transform nuclear magnetic resonance (FT-NMR) for analyzing of carbon atom ( 13 C) using Distortionless Enhancement by Polarization Transfer (DEPT) measurement mode with coupling as well as without coupling from proton atom ( 1 H). Molecular structure analysis result showed that DEPT FT-NMR measurement mode with coupling as well as without coupling from 1 H was very fast, exact and accurate method for molecular analysis of organic compound especially methacryloyl-L-alanine methyl ester. (author)

In vivo regulation of scavenger receptor BI and the selective uptake of high density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer cells

NARCIS (Netherlands)

Fluiter, K.; van der Westhuijzen, D. R.; van Berkel, T. J.

1998-01-01

High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL

Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

Science.gov (United States)

Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

2013-12-01

Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis

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Shu-xia Guo

2016-09-01

Full Text Available Background: Previous studies have evaluated the associations between the cholesteryl ester transfer protein (CETP TaqIB polymorphism (rs708272, the risk of developing composite ischemic cardiovascular disease (CVD and the concentration of high-density lipoprotein cholesterol (HDL-C, but results remain controversial. The objective of this study was to investigate whether a relationship exists between these factors. Methods: We conducted a meta-analysis of available studies to clarify the associations of the CETP TaqIB polymorphism with HDL-C concentration and the composite ischemic CVD risk in both Asians and Caucasians. All statistical analyses were done with Stata 12.0. Results: Through utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer, China Science and Technology Journal Database, China National Knowledge Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44 papers with 20,866 cases and 21,298 controls were combined showing a significant association between the CETP TaqIB variant and composite ischemic CVD risk. Carriers of allele TaqIB-B1 were found to have a higher risk of composite ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09–1.21, p < 0.001. Meanwhile, 28 studies with 23,959 subjects were included in the association between the CETP TaqIB polymorphism and the concentration of HDL-C. Results suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36–0.65, p < 0.001. Conclusions: The synthesis of available evidence demonstrates that the CETP TaqIB polymorphism protects against composite ischemic CVD risk and is associated with a higher HDL-C concentration in both Asians and Caucasians.

Mechanical properties and chemical stability of pivalolactone-based poly(ether ester)s

NARCIS (Netherlands)

Tijsma, E.J.; Tijsma, E.J.; van der Does, L.; Bantjes, A.; Bantjes, A.; Vulic, I.

1994-01-01

The processing, mechanical and chemical properties of poly(ether ester)s, prepared from pivalolactone (PVL), 1,4-butanediol (4G) and dimethyl terephthalate (DMT), were studied. The poly(ether ester)s could easily be processed by injection moulding, owing to their favourable rheological and thermal

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.

Science.gov (United States)

Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Hegele, Robert A; Lewis, Gary F

2016-07-01

Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

International Nuclear Information System (INIS)

Wilson, M.D.

1985-01-01

The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension

NARCIS (Netherlands)

Ligtenberg, JJM; vanTol, A; vanHaeften, TW; Sluiter, WJ; Dullaart, RPF

1996-01-01

Objectives. Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key

Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus : modification by triglycerides and cholesteryl ester transfer protein

NARCIS (Netherlands)

Kappelle, Paul J.W.H.; Zwang, Louwerens; Huisman, Menno V.; Banga, Jan Dirk; Sluiter, Wim. J.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

Objectives: Non-HDL-cholesterol (non-HDL-C) and apolipoprotein (apo) B are proposed as treatment targets. The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes. Methods: Analyses were performed in 217 hypertriglyceridaemic type 2

The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading

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Anna Baulies

2018-04-01

Full Text Available Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC, by depleting mitochondrial GSH (mGSH due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC and SLC25A11 (2-oxoglutarate carrier, OGC have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment. Keywords: Cholesterol

Amperometric cholesterol biosensor based on in situ reconstituted cholesterol oxidase on an immobilized monolayer of flavin adenine dinucleotide cofactor.

Science.gov (United States)

Vidal, Juan-C; Espuelas, Javier; Castillo, Juan-R

2004-10-01

A new amperometric biosensor for determining cholesterol based on deflavination of the enzyme cholesterol oxidase (ChOx) and subsequent reconstitution of the apo-protein with a complexed flavin adenine dinucleotide (FAD) monolayer is described. The charge transfer mediator pyrroquinoline quinone (PQQ) was covalently bound to a cystamine self-assembled monolayer (SAM) on an Au electrode. Boronic acid (BA) was then bound to PQQ using the carbodiimide procedure, and the BA ligand was complexed to the FAD molecules on which the apo-ChOx was subsequently reconstituted. The effective release of the FAD from the enzyme and the successful reconstitution were verified using molecular fluorescence and cyclic voltammetry. The optimal orientation of FAD toward the PQQ mediator and the distances between FAD and PQQ and between PQQ and electrode enhance the charge transfer, very high sensitivity (about 2,500 nAmM(-1)cm(-2)) being obtained for cholesterol determination. The biosensor is selective toward electroactive interferents (ascorbic acid and uric acid) and was tested in reference serum samples, demonstrating excellent accuracy (relative errors below 3% in all cases). The biosensor activity can be successfully regenerated in a simple process by successive reconstitution with batches of recently prepared apo-ChOx on the same immobilized Au/SAM-PQQ-BA-FAD monolayer (it was tested five times); the lifetime of the biosensor is about 45-60 days.

Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

Science.gov (United States)

Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

1991-04-15

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia

NARCIS (Netherlands)

Stitziel, Nathan O.; Fouchier, Sigrid W.; Sjouke, Barbara; Peloso, Gina M.; Moscoso, Alessa M.; Auer, Paul L.; Goel, Anuj; Gigante, Bruna; Barnes, Timothy A.; Melander, Olle; Orho-Melander, Marju; Duga, Stefano; Sivapalaratnam, Suthesh; Nikpay, Majid; Martinelli, Nicola; Girelli, Domenico; Jackson, Rebecca D.; Kooperberg, Charles; Lange, Leslie A.; Ardissino, Diego; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Reilly, Muredach P.; Rader, Daniel J.; de Faire, Ulf; Schunkert, Heribert; Erdmann, Jeanette; Samani, Nilesh J.; Charnas, Lawrence; Altshuler, David; Gabriel, Stacey; Kastelein, John J. P.; Defesche, Joep C.; Nederveen, Aart J.; Kathiresan, Sekar; Hovingh, G. Kees

2013-01-01

Objective Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

Haan, W. de; Vries-van der Weij, J. de; Hoorn, J.W.A. van der; Gautier, T.; Hoogt, C.C. van der; Westerterp, M.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

2008-01-01

BACKGROUND - Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, Jose W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Background-Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even

Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin

NARCIS (Netherlands)

de Haan, Willeke; de Vries-van der Weij, Jitske; van der Hoorn, José W. A.; Gautier, Thomas; van der Hoogt, Caroline C.; Westerterp, Marit; Romijn, Johannes A.; Jukema, J. Wouter; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

2008-01-01

Although cholesteryl ester transfer protein (CETP) inhibition is regarded as a promising strategy to reduce atherosclerosis by increasing high-density lipoprotein cholesterol, the CETP inhibitor torcetrapib given in addition to atorvastatin had no effect on atherosclerosis and even increased

Genetic variants in CETP increase risk of intracerebral hemorrhage

NARCIS (Netherlands)

Anderson, C.D.; Falcone, G.J.; Phuah, C.L.; Radmanesh, F.; Brouwers, H.B.; Battey, T.W.; Biffi, A.; Peloso, G.M.; Liu, D.J.; Ayres, A.M.; Goldstein, J.N.; Viswanathan, A.; Greenberg, S.M.; Selim, M.; Meschia, J.F.; Brown, D.L.; Worrall, B.B.; Silliman, S.L.; Tirschwell, D.L.; Flaherty, M.L.; Kraft, P.; Jagiella, J.M.; Schmidt, H.; Hansen, B.M.; Jimenez-Conde, J.; Giralt-Steinhauer, E.; Elosua, R.; Cuadrado-Godia, E.; Soriano, C.; Nieuwenhuizen, K.M. van; Klijn, C.J.M.; Rannikmae, K.; Samarasekera, N.; Salman, R.A.; Sudlow, C.L.; Deary, I.J.; Morotti, A.; Pezzini, A.; Pera, J.; Urbanik, A.; Pichler, A.; Enzinger, C.; Norrving, B.; Montaner, J.; Fernandez-Cadenas, I.; Delgado, P.; Roquer, J.; Lindgren, A.; Slowik, A.; Schmidt, R.; Kidwell, C.S.; Kittner, S.J.; Waddy, S.P.; Langefeld, C.D.; Abecasis, G.; Willer, C.J.; Kathiresan, S.; Woo, D.; Rosand, J.

2016-01-01

OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

Genetic variants in CETP increase risk of intracerebral hemorrhage

NARCIS (Netherlands)

Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W K; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J.; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M.; Klijn, Catharina J M; Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al Shahi; Sudlow, Catherine L.; Deary, Ian J.; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Kidwell, Chelsea S.; Kittner, Steven J.; Waddy, Salina P.; Langefeld, Carl D.; Abecasis, Goncalo; Willer, Cristen J.; Kathiresan, Sekar; Woo, Daniel; Rosand, Jonathan

2016-01-01

Objective: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

NARCIS (Netherlands)

Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

1998-01-01

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels

What's Cholesterol?

Science.gov (United States)

... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

Glycosidic Bond Cleavage is Not Required for Phytosteryl Glycoside-Induced Reduction of Cholesterol Absorption in Mice

Science.gov (United States)

Lin, Xiaobo; Ma, Lina; Moreau, Robert A.

2012-01-01

Phytosteryl glycosides occur in natural foods but little is known about their metabolism and bioactivity. Purified acylated steryl glycosides (ASG) were compared with phytosteryl esters (PSE) in mice. Animals on a phytosterol-free diet received ASG or PSE by gavage in purified soybean oil along with tracers cholesterol-d7 and sitostanol-d4. In a three-day fecal recovery study, ASG reduced cholesterol absorption efficiency by 45 ± 6% compared with 40 ± 6% observed with PSE. Four hours after gavage, plasma and liver cholesterol-d7 levels were reduced 86% or more when ASG was present. Liver total phytosterols were unchanged after ASG administration but were significantly increased after PSE. After ASG treatment both ASG and deacylated steryl glycosides (SG) were found in the gut mucosa and lumen. ASG was quantitatively recovered from stool samples as SG. These results demonstrate that ASG reduces cholesterol absorption in mice as efficiently as PSE while having little systemic absorption itself. Cleavage of the glycosidic linkage is not required for biological activity of ASG. Phytosteryl glycosides should be included in measurements of bioactive phytosterols. PMID:21538209

Development of solvent-free offset ink using vegetable oil esters and high molecular-weight resin.

Science.gov (United States)

Park, Jung Min; Kim, Young Han; Kim, Sung Bin

2013-01-01

In the development of solvent-free offset ink, the roles of resin molecular weight and used solvent on the ink performance were evaluated by examining the relationship between the various properties of resin and solvent and print quality. To find the best performing resin, the soy-oil fatty acid methyl ester (FAME) was applied to the five modified-phenolic resins having different molecular weights. It is found from the experimental results that the ink made of higher molecular weight and better solubility resin gives better printability and print quality. It is because larger molecular weight resin with better solubility gives higher rate of ink transfer. From the ink application of different esters to high molecular weight resin, the best printing performance was yielded from the soy-oil fatty acid butyl ester (FABE). It is due to its high kinematic viscosity resulting in the smallest change of ink transfer weight upon multiple number of printing, which improves the stability of ink quality.

The sonochemical arylation of malonic esters mediated by manganese triacetate.

Science.gov (United States)

Meciarova, M; Toma, S; Luche, J L

2001-04-01

The intermolecular arylation of malonate esters in acetic acid solution in the presence of manganese(III) triacetate is known to proceed via an Electron Transfer mechanism. Under sonication, this reaction undergoes only minor changes. In contrast, the intramolecular reaction of dimethyl alpha-(3-phenylpropyl)malonate provides a new case of sonochemical switching, with the formation of compounds 7-9, while conventional thermal conditions generate only the bicyclic compound 6. Reactions using the more powerful oxidant, cerium ammonium nitrate are governed by the formation of the nitrate ester 11. Compounds 7-9 are isolated in yields lower than with MnTA, and in proportions depending on the conditions, thermal or sonochemical.

Liquid Crystalline Thermosets from Ester, Ester-imide, and Ester-amide Oligomers

Science.gov (United States)

Dingemans, Theodorus J. (Inventor); Weiser, Erik S. (Inventor); St. Clair, Terry L. (Inventor)

2009-01-01

Main chain thermotropic liquid crystal esters, ester-imides, and ester-amides were prepared from AA, BB, and AB type monomeric materials and end-capped with phenylacetylene, phenylmaleimide, or nadimide reactive end-groups. The end-capped liquid crystal oligomers are thermotropic and have, preferably, molecular weights in the range of approximately 1000-15,000 grams per mole. The end-capped liquid crystaloligomers have broad liquid crystalline melting ranges and exhibit high melt stability and very low melt viscosities at accessible temperatures. The end-capped liquid crystal oli-gomers are stable forup to an hour in the melt phase. They are highly processable by a variety of melt process shape forming and blending techniques. Once processed and shaped, the end-capped liquid crystal oigomers were heated to further polymerize and form liquid crystalline thermosets (LCT). The fully cured products are rubbers above their glass transition temperatures.

The role of CETP inhibition in dyslipidemia

NARCIS (Netherlands)

El Harchaoui, Karim; van der Steeg, Wim A.; Stroes, Erik S. G.; Kastelein, John J. P.

2007-01-01

Cholesteryl ester transfer protein (CETP) inhibitors are currently being investigated because of their ability to increase high-density lipoprotein cholesterol levels. In various metabolic settings, the relationship between CETP and lipoprotein metabolism is complex and may depend largely on the

Influence of molecular packing and phospholipid type on rates of cholesterol exchange

International Nuclear Information System (INIS)

Lund-Katz, S.; Laboda, H.M.; McLean, L.R.; Phillips, M.C.

1988-01-01

The rates of [ 14 C]cholesterol transfer from small unilamellar vesicles containing cholesterol dissolved in bilayers of different phospholipids have been determined to examine the influence of phospholipid-cholesterol interactions on the rate of cholesterol desorption from the lipid-water interface. At 37 0 C, for vesicles containing 10 mol % cholesterol, the half-times for exchange are about 1, 13, and 80 h, respectively, for unsaturated PC, saturated PC, and SM. In order to probe how differences in molecular packing in the bilayers cause the rate constants for cholesterol desorption to be in the order unsaturated PC > saturated PC > SM, nuclear magnetic resonance (NMR) and monolayer methods were used to evaluate the cholesterol physical state and interactions with phospholipid. The NMR relaxation parameters for [4- 13 C] cholesterol reveal no differences in molecular dynamics in the above bilayers. The greater van der Waals interaction in the SM monolayer (or bilayer) compared to PC gives rise to a larger condensation by cholesterol. This is a direct demonstration of the greater interaction of cholesterol with SM compared to PC. An estimate of the van der Waals interactions between cholesterol and these phospholipids has been used to derive a relationship between the ratio of the rate constants for cholesterol desorption and the relative molecular areas (lateral packing density) in two bilayers. This analysis suggests that differences in cholesterol-phospholipid van der Waals interaction energy are an important cause of varying rates of cholesterol exchange from different host phospholipid bilayers

Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related Susceptibility to Cognitive Deficits in Type 2 Diabetic Patients.

Science.gov (United States)

Sun, Jie; Cai, Rongrong; Huang, Rong; Wang, Pin; Tian, Sai; Sun, Haixia; Xia, Wenqing; Wang, Shaohua

2016-08-01

Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.

Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apoA-I from murine RAW 264.7 macrophages

Directory of Open Access Journals (Sweden)

Allen Anne Marie

2012-12-01

Full Text Available Abstract Background Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. Methods Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett’s or Bonferroni post t-tests, as appropriate. Results The positive control, resveratrol (24 h, significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 μM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; ppAbca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 μM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1 and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2, indicating profound dysregulation of cholesterol homeostasis. Conclusions Acute loss of mitochondrial function, and in particular Δψm, reduces

Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk

NARCIS (Netherlands)

Ference, Brian A.; Kastelein, John J. P.; Ginsberg, Henry N.; Chapman, M. John; Nicholls, Stephen J.; Ray, Kausik K.; Packard, Chris J.; Laufs, Ulrich; Brook, Robert D.; Oliver-Williams, Clare; Butterworth, Adam S.; Danesh, John; Smith, George Davey; Catapano, Alberico L.; Sabatine, Marc S.

2017-01-01

IMPORTANCE Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered. OBJECTIVE To estimate the association

What Is Cholesterol?

Science.gov (United States)

... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

Reference intervals for serum total cholesterol, HDL cholesterol and ...

African Journals Online (AJOL)

Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

Catalytic Ester to Stannane Functional Group Interconversion via Decarbonylative Cross-Coupling of Methyl Esters

KAUST Repository

Yue, Huifeng

2018-01-03

An unprecedented conversion of methyl esters to stannanes was realized, providing access to a series of arylstannanes via nickel catalysis. Various common esters including ethyl, cyclohexyl, benzyl, and phenyl esters can undergo the newly developed decarbonylative stannylation reaction. The reaction shows broad substrate scope, can differentiate between different types of esters, and if applied in consecutive fashion, allows the transformation of methyl esters into aryl fluorides or biaryls via fluororination or arylation.

Catalytic Ester to Stannane Functional Group Interconversion via Decarbonylative Cross-Coupling of Methyl Esters

KAUST Repository

Yue, Huifeng; Zhu, Chen; Rueping, Magnus

2018-01-01

An unprecedented conversion of methyl esters to stannanes was realized, providing access to a series of arylstannanes via nickel catalysis. Various common esters including ethyl, cyclohexyl, benzyl, and phenyl esters can undergo the newly developed decarbonylative stannylation reaction. The reaction shows broad substrate scope, can differentiate between different types of esters, and if applied in consecutive fashion, allows the transformation of methyl esters into aryl fluorides or biaryls via fluororination or arylation.

Levels of cholesteryl esters and other lipids in the plasma of patientswith end-stage renal failure

International Nuclear Information System (INIS)

Gillett, Michael P.T.; Obineche, Enyioma N.; Lakhani, Mohammad S.; Abdulle, Abdishakur M.; Amirlak, I.; Al-Rukhaimi, M.; Suleiman, Mustafa N.

2001-01-01

The importance of plasma lipid abnormalities in chronic renal failure(CRF) is well recognized, but surprisingly little attention has been given tothe study of some plasma lipid fractions, including cholesteryl esters (CE)and phospholipids, which might be expected to be important factors in thepathogenesis of disease. Fasting blood samples were taken from 25 controlsubjects and 53 CRF patients (29 predialysis and 24 on Hemodialysis). Sampleswere analyzed for urea nitrogen, creatinine, triacyglycerols, total andindividuals phospholipids, total and free cholesterol, as well as cholesterolbound to be very low-, and high- density lipoproteins (VDL, LDL and HDL).Plasma CE was calculated and expressed as a percentage of total cholesterol.Over half of the patients had CE levels more than two standard deviationsbelow the control value. In this subgroup of low CE patients, total LDL- andHDL-cholesterol levels were also significantly lower than for controls, whilelevels of phosphatidylcholine and lysophosphatidylcholine were decreased andincreased, respectively. In patients with high CE, no significant lipidabnormalities were observed. In this study, CE was an excellent marker forlipid disturbances-if CE was high, then the other lipid fractions wereabnormal. The changes noted appear to be consequences of or related todeficiency of the plasma enzyme lecithin-cholesterol acyltransferase. (author)

Insight into solid-liquid phase transfer catalyzed synthesis of ...

Indian Academy of Sciences (India)

Ganapati D Yadav

2017-11-16

Nov 16, 2017 ... Mecoprop ester using K2CO3 as base and development of new kinetic model ... acid family.1 Several salts and esters of Mecoprop are used as active ..... Influence of mass transfer was determined by varying the stirring speed ...

Sensibilization of escherichia coli cells by cholesterol incorporated into their membrane

International Nuclear Information System (INIS)

Breslev, S.E.; Rozenberg, O.A.; Noskin, L.A.; Stepanova, I.M.; Beketova, A.G.; Loshakova, L.V.; Kovaleva, I.G.

1984-01-01

It has been established earlier that a level of cell radiosensitivity is defined by membrane viscosity changing in a wide temperature range. Therefore in epsilon coli cells of a natural type lethal doses of gamma rays are increased approximately a 3.5 times at 45 deg C, as compared to 4 deg C. Cholesterol changing a phase state of membrane lipids was used as a modifying factor. Liposomes were used with the goal of effective bacteria transfer to a membrane. It is established that liposomes without cholesterol do not affect their radioresistance and an increase of its content leads to resistance decrease. The effect is attained only at a sufficient long time of incubation of cells with liposomes (10-16 h). At 4 deg C lipids of E. coli membrane are in a solid-crystalline state independently on pholesterol presence, because of this, radiosensitivity does not change. Temperature increase up to 45 deg C transfer a part of lipids to a liquid-crystalline state, thus decreasing membrane viscosity. In this case cholesterol manifests itself. The authors explain viscosity increase with a violation in functioning of those enzyme systems, which activity is connected with membrane structural state, including enzymes of DNA repair. The authors assume that the radiosensibilization effect of cholesterol introduction into a bacterial membrane in high-temperature cell irradiation is explained by this phenomenon

Cholesterol-dependent energy transfer between fluorescent proteins-insights into protein proximity of APP and BACE1 in different membranes in Niemann-Pick type C disease cells.

Science.gov (United States)

von Einem, Bjoern; Weber, Petra; Wagner, Michael; Malnar, Martina; Kosicek, Marko; Hecimovic, Silva; Arnim, Christine A F von; Schneckenburger, Herbert

2012-11-26

Förster resonance energy transfer (FRET) -based techniques have recently been applied to study the interactions between β-site APP-cleaving enzyme-GFP (BACE1-GFP) and amyloid precursor protein-mRFP (APP-mRFP) in U373 glioblastoma cells. In this context, the role of APP-BACE1 proximity in Alzheimer's disease (AD) pathogenesis has been discussed. FRET was found to depend on intracellular cholesterol levels and associated alterations in membrane stiffness. Here, NPC1 null cells (CHO-NPC1-/-), exhibiting increased cholesterol levels and disturbed cholesterol transport similar to that observed in Niemann-Pick type C disease (NPC), were used to analyze the influence of altered cholesterol levels on APP-BACE1 proximity. Fluorescence lifetime measurements of whole CHO-wild type (WT) and CHO-NPC1-/- cells (EPI-illumination microscopy), as well as their plasma membranes (total internal reflection fluorescence microscopy, TIRFM), were performed. Additionally, generalized polarization (GP) measurements of CHO-WT and CHO-NPC1-/- cells incubated with the fluorescence marker laurdan were performed to determine membrane stiffness of plasma- and intracellular-membranes. CHO-NPC1-/- cells showed higher membrane stiffness at intracellular- but not plasma-membranes, equivalent to cholesterol accumulation in late endosomes/lysosomes. Along with higher membrane stiffness, the FRET efficiency between BACE1-GFP and APP-mRFP was reduced at intracellular membranes, but not within the plasma membrane of CHO-NPC1-/-. Our data show that FRET combined with TIRF is a powerful technique to determine protein proximity and membrane fluidity in cellular models of neurodegenerative diseases.

LDL-C levels in older people: Cholesterol homeostasis and the free radical theory of ageing converge.

Science.gov (United States)

Mc Auley, Mark T; Mooney, Kathleen M

2017-07-01

The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations. We hypothesize that the free radical theory of ageing (FRTA) together with disrupted cholesterol homeostasis can account for these observations. Based on this hypothesis, dysregulated hepatic cholesterol homeostasis in older people is characterised by two distinct metabolic states. The first state accounts for an older person who has elevated plasma LDL-C. This state is underpinned by the FRTA which suggests there is a decrease in cellular antioxidant capacity with age. This deficiency enables hepatic reactive oxidative species (ROS) to induce the total activation of HMG-CoA reductase, the key rate limiting enzyme in cholesterol biosynthesis. An increase in cholesterol synthesis elicits a corresponding rise in LDL-C, due to the downregulation of LDL receptor synthesis, and increased production of very low density lipoprotein cholesterol (VLDL-C). In the second state of dysregulation, ROS also trigger the total activation of HMG-CoA reductase. However, due to an age associated decrease in the activity of cholesterol-esterifying enzyme, acyl CoA: cholesterol acyltransferase, there is restricted conversion of excess free cholesterol (FC) to cholesterol esters. Consequently, the secretion of VLDL-C drops, and there is a corresponding decrease in LDL-C. As intracellular levels of FC accumulate, this state progresses to a pathophysiological condition akin to nonalcoholic fatty liver disease. It is our

Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand

Directory of Open Access Journals (Sweden)

Hanna Tukachinsky

2012-08-01

Full Text Available The Hedgehog (Hh signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand.

Gamma radiolysis and vinyl esters

International Nuclear Information System (INIS)

De Bruyn, H.; Balic, R.; Gilbert, R.G.

1998-01-01

The principle behind γ relaxation of free-radical polymerizations is that the source of initiating radicals can be switched off 'instantaneously'. In the absence of initiating radicals the only kinetic events remaining are propagation, transfer and termination. For monomers whose propagation rate coefficients have been determined, relaxation behaviour can be interpreted to determine radical-loss rate coefficients and test models of loss mechanisms. This technique has been employed successfully on styrene and MMA emulsion polymerizations. In the present study, vinyl acetate and vinyl neo-decanoate (a ten-carbon-branched homologue of vinyl acetate) were studied, with the propagation rate coefficients for both monomers being established by pulsed-laser polymerization. Both were found to exhibit rapid γ relaxation rates in emulsion polymerization. This is a surprising result because mechanisms for rapid relaxation in emulsion polymerizations require that chain transfer to monomer (which is rapid for both monomers) is followed by exit from the particle into the aqueous phase with subsequent re-entry into a radical-containing particle leading to bimolecular termination. It is not unreasonable to suppose that this may be possible for vinyl acetate which is fairly water soluble (∼0.3 M). However, vinyl neo-decanoate is virtually insoluble (∼0.00004 M) and hence desorption is extremely unlikely. The most likely explanation for the observed rapid relaxations is that some of the radicals produced by γ radiolysis are slow to initiate vinyl esters and hence act as radical traps. As vinyl esters are known to be particularly unreactive monomers. it is feasible that this experimental artifact affects them to a much greater extent than some of the monomers studied successfully with this technique in the past

Use of dansyl-cholestanol as a probe of cholesterol behavior in membranes of living cells[S

Science.gov (United States)

Huang, Huan; McIntosh, Avery L.; Atshaves, Barbara P.; Ohno-Iwashita, Yoshiko; Kier, Ann B.; Schroeder, Friedhelm

2010-01-01

While plasma membrane cholesterol-rich microdomains play a role in cholesterol trafficking, little is known about the appearance and dynamics of cholesterol through these domains in living cells. The fluorescent cholesterol analog 6-dansyl-cholestanol (DChol), its biochemical fractionation, and confocal imaging of L-cell fibroblasts contributed the following new insights: i) fluorescence properties of DChol were sensitive to microenvironment polarity and mobility; (ii) DChol taken up by L-cell fibroblasts was distributed similarly as cholesterol and preferentially into cholesterol-rich vs. -poor microdomains resolved by affinity chromatography of purified plasma membranes; iii) DChol reported similar polarity (dielectric constant near 18) but higher mobility near phospholipid polar head group region for cholesterol in purified cholesterol-rich versus -poor microdomains; and iv) real-time confocal imaging, quantitative colocalization analysis, and fluorescence resonance energy transfer with cholesterol-rich and -poor microdomain markers confirmed that DChol preferentially localized in plasma membrane cholesterol-rich microdomains of living cells. Thus, DChol sensed a unique, relatively more mobile microenvironment for cholesterol in plasma membrane cholesterol-rich microdomains, consistent with the known, more rapid exchange dynamics of cholesterol from cholesterol-rich than -poor microdomains. PMID:20008119

JTT-130, a microsomal triglyceride transfer protein (MTP inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

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Shrestha Sudeep

2005-09-01

Full Text Available Abstract Background Microsomal transfer protein inhibitors (MTPi have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG. However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control, 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats

International Nuclear Information System (INIS)

Kim, Soon-Ja; Bok, Song-Hae; Lee, Sangku; Kim, Hye-Jin; Lee, Mi-Kyung; Park, Yong Bok; Choi, Myung-Sook

2005-01-01

Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (L-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (L-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity

CoMFA, CoMSIA and Eigenvalue Analysis on Dibenzodioxepinone and Dibenzodioxocinone Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

Directory of Open Access Journals (Sweden)

Mao-sheng Cheng

2008-08-01

Full Text Available Abstract: CoMFA, CoMSIA and eigenvalue analysis (EVA were performed to study the structural features of 61 diverse dibenzodioxepinone and dibenzodioxocinone analogues to probe cholesteryl ester transfer protein (CETP inhibitory activity. Three methods yielded statistically significant models upon assessment of cross-validation, bootstrapping, and progressive scrambling. This was further validated by an external set of 13 derivatives. Our results demonstrate that three models have a good interpolation as well as extrapolation. The hydrophobic features were confirmed to contribute significantly to inhibitor potencies, while a pre-oriented hydrogen bond provided by the hydroxyl group at the 3-position indicated a good correlation with previous SAR, and a hydrogen bond acceptor may play a crucial role in CETP inhibition. These derived models may help us to gain a deeper understanding of the binding interaction of these lactone-based compounds and aid in the design of new potent compounds against CETP.

Esters with water esters 2-c to 6-c

CERN Document Server

Getzen, F W; Hefter, G T; Maczynski, Andrzej

1992-01-01

This volume is the first of two devoted to esters and water. It includes solubility data for binary systems containing an ester and water up to the end of 1988. The critical evaluations were all prepared by one author and an introductory section has been included to elaborate the philosophy and methodology followed in the evaluations.

Synthesis and characterization of a novel rhodamine labeled cholesterol reporter.

Science.gov (United States)

Maiwald, Alexander; Bauer, Olivia; Gimpl, Gerald

2017-06-01

We introduce the novel fluorescent cholesterol probe RChol in which a sulforhodamine group is linked to the sixth carbon atom of the steroid backbone of cholesterol. The same position has recently been selected to generate the fluorescent reporter 6-dansyl-cholestanol (DChol) and the photoreactive 6-azi-cholestanol. In comparison with DChol, RChol is brighter, much more photostable, and requires less energy for excitation, i.e. favorable conditions for microscopical imaging. RChol easily incorporates into methyl-β-cyclodextrin forming a water-soluble inclusion complex that acts as an efficient sterol donor for cells and membranes. Like cholesterol, RChol possesses a free 3'OH group, a prerequisite to undergo intracellular esterification. RChol was also able to support the growth of cholesterol auxotrophic cells and can therefore substitute for cholesterol as a major component of the plasma membrane. According to subcellular fractionation, slight amounts of RChol (~12%) were determined in low-density Triton-insoluble fractions whereas the majority of RChol was localized in non-rafts fractions. In phase-separated giant unilamellar vesicles, RChol preferentially partitions in liquid-disordered membrane domains. Intracellular RChol was transferred to extracellular sterol acceptors such as high density lipoproteins in a dose-dependent manner. Unlike DChol, RChol was not delivered to the cholesterol storage pathway. Instead, it translocated to endosomes/lysosomes with some transient contacts to peroxisomes. Thus, RChol is considered as a useful probe to study the endosomal/lysosomal pathway of cholesterol. Copyright © 2017 Elsevier B.V. All rights reserved.

Avocado and olive oil methyl esters

International Nuclear Information System (INIS)

Knothe, Gerhard

2013-01-01

Biodiesel, the mono-alkyl esters of vegetable oils, animal fats or other triacylglycerol-containing materials and an alternative to conventional petroleum-based diesel fuel, has been derived from a variety of feedstocks. Numerous feedstocks have been investigated as potential biodiesel sources, including commodity oils, however, the methyl esters of avocado and olive oil would likely be suitable as biodiesel fuel. In order to expand the database and comprehensive evaluation of the properties of vegetable oil esters, in this work the fuel-related properties of avocado and olive oil methyl esters, which exhibit similar fatty acid profiles including high oleic acid content, are determined. The cetane numbers of avocado oil methyl esters and olive oil methyl esters are relatively high, determined as 59.2 and 62.5, respectively, due to their elevated content of methyl oleate. Other properties are well within the ranges specified in biodiesel standards. The cloud points of both esters are slightly above 0 °C due to their content of saturated esters, especially methyl palmitate. Overall, avocado and olive oil yield methyl esters with fuel properties comparable to methyl esters from other commodity vegetable oils. The 1 H and 13 C NMR spectra of avocado and olive oil methyl esters are reported. -- Highlights: • Methyl esters of avocado and olive oil meet biodiesel fuel standards. • Provides comparison for methyl esters of other vegetable oils with high oleic content. • Discusses and compares present results with prior literature

Heat transfer coefficient as parameter describing ability of insulating liquid to heat transfer

Science.gov (United States)

Nadolny, Zbigniew; Gościński, Przemysław; Bródka, Bolesław

2017-10-01

The paper presents the results of the measurements of heat transfer coefficient of insulating liquids used in transformers. The coefficient describes an ability of the liquid to heat transport. On the basis of the coefficient, effectiveness of cooling system of electric power devices can be estimated. Following liquids were used for the measurements: mineral oil, synthetic ester and natural ester. It was assumed that surface heat load is about 2500 W·m-2, which is equal the load of transformer windings. A height of heat element was 1.6 m, because it makes possible steady distribution of temperature on its surface. The measurements of heat transfer coefficient was made as a function of various position of heat element (vertical, horizontal). In frame of horizontal position of heat element, three suppositions were analysed: top, bottom, and side.

Heat transfer coefficient as parameter describing ability of insulating liquid to heat transfer

Directory of Open Access Journals (Sweden)

Nadolny Zbigniew

2017-01-01

Full Text Available The paper presents the results of the measurements of heat transfer coefficient of insulating liquids used in transformers. The coefficient describes an ability of the liquid to heat transport. On the basis of the coefficient, effectiveness of cooling system of electric power devices can be estimated. Following liquids were used for the measurements: mineral oil, synthetic ester and natural ester. It was assumed that surface heat load is about 2500 W·m-2, which is equal the load of transformer windings. A height of heat element was 1.6 m, because it makes possible steady distribution of temperature on its surface. The measurements of heat transfer coefficient was made as a function of various position of heat element (vertical, horizontal. In frame of horizontal position of heat element, three suppositions were analysed: top, bottom, and side.

Cholesterol testing and results

Science.gov (United States)

... your cholesterol is in this normal range. LDL (Bad) Cholesterol LDL cholesterol is sometimes called "bad" cholesterol. ... to 3.3 mmol/l) are desired. VLDL (Bad) Cholesterol VLDL contains the highest amount of triglycerides. ...

Cholesterol Facts and Statistics

Science.gov (United States)

... Managing High Cholesterol Cholesterol-lowering Medicine High Cholesterol Statistics and Maps High Cholesterol Facts High Cholesterol Maps ... Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart ...

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

OpenAIRE

Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

2009-01-01

Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

Dispatched and scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand.

Science.gov (United States)

Tukachinsky, Hanna; Kuzmickas, Ryan P; Jao, Cindy Y; Liu, Jing; Salic, Adrian

2012-08-30

The Hedgehog (Hh) signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp) and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

International Nuclear Information System (INIS)

Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

1990-01-01

The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [ 14 C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans

Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

Directory of Open Access Journals (Sweden)

Jin Gang

2009-10-01

Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1).

Science.gov (United States)

Al-Daghri, Nasser M; Alharbi, Mohammed; Wani, Kaiser; Abd-Alrahman, Sherif H; Sheshah, Eman; Alokail, Majed S

2015-01-01

Thiamine (vitamin B1) is an essential enzyme cofactor in most organisms required at several stages of anabolic and catabolic intermediary metabolism. However, little is known on the positive effects of thiamine in diabetic type 1 (DMT1) patients. The objectives of this study were to evaluate the biochemical changes related to thiamine deficiency in patients with DMT1 outcomes among Saudi adults. We hypothesized that blood thiamine deficiency in patients with DMT1 manifestations might lead to an increase in metabolic syndrome. A total of 77 patients with DMT1 (age 35.8 ± 5.5) and 81 controls (age 45.0 ± 18.1) (total N = 158) were randomly selected from the Riyadh Cohort Study for inclusion. Saudi adults with diabetes type 1, a significant decrease in systolic (P < 0.001), and diastolic blood pressure (P = 0.008) and microalbuminuria (P = 0.02). Moreover, cholesterol, glucose and triglycerides were significantly increased (P 0.001, 0.001 and 0.008, respectively) in patients with diabetes type 1 compared to controls. On the other hand, HDL, TMP, TDP and thiamine, were significantly decreased in patients with diabetes type 1 (P 0.005, 0.002, 0.005, and 0.002), respectively. A strong association between blood thiamine level and diabetes type 1 was detected in our study population. The results confirmed the role of thiamine and thiamine phosphate esters, in preventing metabolic changes and complications of diabetes type 1. The levels of these thiamine and thiamine phosphate esters were correlated with diabetes related biomarkers including HDL, glucose, triglycerides and cholesterol, as well as microalbuminuria, LDL and urine thiamine. The results support a pivotal role of blood thiamine and its phosphate esters in preventing the biochemical changes and complications in patients with DMT1.

Oxysterol-Binding Protein-Related Protein 1L Regulates Cholesterol Egress from the Endo-Lysosomal System

Directory of Open Access Journals (Sweden)

Kexin Zhao

2017-05-01

Full Text Available Lipoprotein cholesterol is delivered to the limiting membrane of late endosomes/lysosomes (LELs by Niemann-Pick C1 (NPC1. However, the mechanism of cholesterol transport from LELs to the endoplasmic reticulum (ER is poorly characterized. We report that oxysterol-binding protein-related protein 1L (ORP1L is necessary for this stage of cholesterol export. CRISPR-mediated knockout of ORP1L in HeLa and HEK293 cells reduced esterification of cholesterol to the level in NPC1 knockout cells, and it increased the expression of sterol-regulated genes and de novo cholesterol synthesis, indicative of a block in cholesterol transport to the ER. In the absence of this transport pathway, cholesterol-enriched LELs accumulated in the Golgi/perinuclear region. Cholesterol delivery to the ER required the sterol-, phosphatidylinositol 4-phosphate-, and vesicle-associated membrane protein-associated protein (VAP-binding activities of ORP1L, as well as NPC1 expression. These results suggest that ORP1L-dependent membrane contacts between LELs and the ER coordinate cholesterol transfer with the retrograde movement of endo-lysosomal vesicles.

Simvastatin promotes NPC1-mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL-loaded macrophages.

Science.gov (United States)

Xu, Xiaoyang; Zhang, Aolin; Halquist, Matthew S; Yuan, Xinxu; Henderson, Scott C; Dewey, William L; Li, Pin-Lan; Li, Ningjun; Zhang, Fan

2017-02-01

Statins, 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, are the first-line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol-lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi-photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low-density lipoprotein but had little effect in reducing the sizes of cholesteryl ester-containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome-compartmentalized cholesterol. Functionally, the egression of free cholesterol from lysosomes attenuated pro-inflammatory cytokine secretion. It was determined that the reduction of lysosomal free cholesterol buildup by simvastatin was due to the up-regulation of Niemann-Pick C1 (NPC1), a lysosomal residing cholesterol transporter. Moreover, the enhanced enzymatic production of 7-hydroxycholesterol by cytochrome P450 7A1 and the subsequent activation of liver X receptor α underscored the up-regulation of NPC1. These findings reveal a novel pleiotropic effect of simvastatin in affecting lysosomal cholesterol efflux in macrophages and the associated significance in the treatment of atherosclerosis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Organization of fluorescent cholesterol analogs in lipid bilayers - lessons from cyclodextrin extraction.

Science.gov (United States)

Milles, Sigrid; Meyer, Thomas; Scheidt, Holger A; Schwarzer, Roland; Thomas, Lars; Marek, Magdalena; Szente, Lajos; Bittman, Robert; Herrmann, Andreas; Günther Pomorski, Thomas; Huster, Daniel; Müller, Peter

2013-08-01

To characterize the structure and dynamics of cholesterol in membranes, fluorescent analogs of the native molecule have widely been employed. The cholesterol content in membranes is in general manipulated by using water-soluble cyclodextrins. Since the interactions between cyclodextrins and fluorescent-labeled cholesterol have not been investigated in detail so far, we have compared the cyclodextrin-mediated membrane extraction of three different fluorescent cholesterol analogs (one bearing a NBD and two bearing BODIPY moieties). Extraction of these analogs was followed by measuring the Förster resonance energy transfer between a rhodamine moiety linked to phosphatidylethanolamine and the labeled cholesterol. The extraction kinetics revealed that the analogs are differently extracted from membranes. We examined the orientation of the analogs within the membrane and their influence on lipid condensation using NMR and EPR spectroscopies. Our data indicate that the extraction of fluorescent sterols from membranes is determined by several parameters, including their impact on lipid order, their hydrophobicity, their intermolecular interactions with surrounding lipids, their orientation within the bilayer, and their affinity with the exogenous acceptor. Copyright © 2013 Elsevier B.V. All rights reserved.

Degradation of Jatropha curcas phorbol esters derived from Jatropha oil cake and their tumor-promoting activity.

Science.gov (United States)

Nakao, Motoyuki; Hasegawa, Go; Yasuhara, Tadashi; Ishihara, Yoko

2015-04-01

Large amount of oil cake is generated during biodiesel production from Jatropha seeds. Although Jatropha oil cake is rich in plant nutrients, presence of toxic phorbol esters restricts the usage of oil cake as a fertilizer. The objective of this study is to evaluate the components and tumor promoting activity of phorbol esters in Jatropha oil cake-supplemented soil and plants grown in the treated soil. Contents and their biological activity of Jatropha phorbol esters in soil and plants were sequentially analyzed by high-performance liquid chromatography (HPLC) and in vitro cell transformation assay, respectively. Disappearance of Jatropha phorbol-ester-specific peaks were followed with HPLC during incubation of Jatropha oil cake with soil for five weeks. Along with the degradation of Jatropha phorbol ester in soil, tumor-promoting activity in the sample was also attenuated and ultimately disappeared. Jatropha phorbol esters and tumor promoting activity were not detected from mustard spinach grown in the Jatropha oil cake-supplemented soil. In addition, the esterase KM109 degrades DHPB (see definition below; Jatropha phorbol ester) and reduced its tumor-promoting activity. From these data, we conclude: (1) components and tumor promoting activity of Jatropha phorbol esters in the oil cake disappeared completely by incubation with soil for five-week, (2) Jatropha phorbol esters did not transfer into plants grown in the Jatropha oil cake-supplemented soil, and (3) DHPB can be degraded by esterase from soil bacterium. These observations are useful for utilization of Jatropha oil cake as a fertilizer. Copyright © 2014 Elsevier Inc. All rights reserved.

MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

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Elisa Balboa

2017-08-01

Full Text Available MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

KAUST Repository

Mandal, Pritam; Noutsi, Bakiza Kamal; Chaieb, Saharoui

2016-01-01

to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration

High blood cholesterol levels

Science.gov (United States)

Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila

Directory of Open Access Journals (Sweden)

Antoine Ducuing

2013-05-01

How morphogen gradients are shaped is a major question in developmental biology, but remains poorly understood. Hedgehog (Hh is a locally secreted ligand that reaches cells at a distance and acts as a morphogen to pattern the Drosophila wing and the vertebrate neural tube. The proper patterning of both structures relies on the precise control over the slope of Hh activity gradient. A number of hypotheses have been proposed to explain Hh movement and hence graded activity of Hh. A crux to all these models is that the covalent binding of cholesterol to Hh N-terminus is essential to achieve the correct slope of the activity gradient. Still, the behavior of cholesterol-free Hh (Hh-N remains controversial: cholesterol has been shown to either increase or restrict Hh range depending on the experimental setting. Here, in fly embryos and wing imaginal discs, we show that cholesterol-free Hh diffuses at a long-range. This unrestricted diffusion of cholesterol-free Hh leads to an absence of gradient while Hh signaling strength remains uncompromised. These data support a model where cholesterol addition restricts Hh diffusion and can transform a leveled signaling activity into a gradient. In addition, our data indicate that the receptor Patched is not able to sequester cholesterol-free Hh. We propose that a morphogen gradient does not necessarily stem from the active transfer of a poorly diffusing molecule, but can be achieved by the restriction of a highly diffusible ligand.

Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

KAUST Repository

Mandal, Pritam

2016-06-01

Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

Cholesterol IQ Quiz

Science.gov (United States)

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Jul 5,2017 Begin the quiz ... What Your Cholesterol Levels Mean Common Misconceptions Cholesterol IQ Quiz • HDL, LDL, and Triglycerides • Causes of High ...

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

Science.gov (United States)

Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

2000-04-01

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

LDL: The "Bad" Cholesterol

Science.gov (United States)

... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

Self-diffusion nuclear magnetic resonance, microstructure transitions, and solubilization capacity of phytosterols and cholesterol in Winsor IV food-grade microemulsions

DEFF Research Database (Denmark)

Spernath, Aviram; Yaghmur, Anan; Aserin, Abraham

2003-01-01

Microemulsions are of growing interest to the food industry as vehicles for delivering and enhancing solubilization of natural food supplements with nutritional and health benefits. The incorporation of molecular phytosterols, cholesterol-lowering agents, in food products is of great interest...... to the food industry. In this work is demonstrated the use of water dilutable food-grade microemulsions consisting of ethoxylated sorbitan ester (Tween 60), water, R-(+)-limonene, ethanol, and propylene glycol as vehicles for enhancing the phytosterols solubilization. Phytosterols were solubilized up to 12...... times more than the dissolution capacity of the oil [R-(+)-limonene] for the same compounds. The solubilization capacity of phytosterols and cholesterol along a dilution line in a pseudo-ternary phase diagram [on this dilution line the weight ratio of R-(+)-limonene/ethanol/Tween 60 is constant at 1...

Home-Use Tests - Cholesterol

Science.gov (United States)

... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

Palladium-catalysed arylation of acetoacetate esters to yield 2-arylacetic acid esters

CSIR Research Space (South Africa)

Zeevaart, JG

2004-05-24

Full Text Available , was developed simultaneously by Hart- wig and Buchwald.5 Typically the tert-butyl ester of propionic acid is treated with an aryl halide (bromide or chloride) in the presence of a strong base, palladium and a bulky phosphine ligand or a bulky imidazolinium CO2t... novel palladium- catalysed conditions for the arylation of acetoacetate esters resulting in the formation of 2-arylacetic acid esters. When we attempted the arylation of tert-butyl aceto- acetate 1a with bromobenzene 2a using mild reaction conditions (K3...

Ester Tuiksoo. Proua Suhkru kibedad päevad / Ester Tuiksoo ; interv. Piret Tali

Index Scriptorium Estoniae

Tuiksoo, Ester, 1965-

2005-01-01

Põllumajandusminister Ester Tuiksoo, kellel peagi täitub ministri ametis aasta Euroopa Liidu suhkrutrahvist, maaettevõtlusest, põllumajandusest, Euroopa Liidu toetustest, ministri elu- ja teenistuskäigust. Lisa: Ester Tuiksoo

Synthetic Methods for Ester Bond Formation and Conformational Analysis of Ester-Containing Carbohydrates

Science.gov (United States)

Hackbusch, Sven

This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general. Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity dependent on the presence or absence of an achiral amine catalyst. In particular, this work establishes a structure-activity relationship with regard to the trans-2-substituent and its role as a chiral auxiliary in the reversal of diastereoselectivity. In the second part, the synthesis of various ester-linked carbohydrate derivatives, and their conformational analysis is presented. Using multidimensional NMR experiments and computational methods, the compounds' solution-phase structures were established and the effect of the ester functional group on the molecules' flexibility and three-dimensional (3D) structure was investigated and compared to ether or glycosidic linkages. To aid in this, a novel Karplus equation for the C(sp2)OCH angle in ester-linked carbohydrates was developed on the basis of a model ester-linked carbohydrate. This equation describes the sinusoidal relationship between the C(sp2)OCH dihedral angle and the corresponding 3JCH coupling constant that can be determined from a J-HMBC NMR experiment. The insights from this research will be useful in describing the 3D structure of naturally occurring and lab-made ester-linked derivatives of carbohydrates, as well as guiding the de novo-design of

Environmental effect of rapeseed oil ethyl ester

International Nuclear Information System (INIS)

Makareviciene, V.; Janulis, P.

2003-01-01

Exhaust emission tests were conducted on rapeseed oil methyl ester (RME), rapeseed oil ethyl ester (REE) and fossil diesel fuel as well as on their mixtures. Results showed that when considering emissions of nitrogen oxides (NO x ), carbon monoxide (CO) and smoke density, rapeseed oil ethyl ester had less negative effect on the environment in comparison with that of rapeseed oil methyl ester. When fuelled with rapeseed oil ethyl ester, the emissions of NO x showed an increase of 8.3% over those of fossil diesel fuel. When operated on 25-50% bio-ester mixed with fossil diesel fuel, NO x emissions marginally decreased. When fuelled with pure rapeseed oil ethyl ester, HC emissions decreased by 53%, CO emissions by 7.2% and smoke density 72.6% when compared with emissions when fossil diesel fuel was used. Carbon dioxide (CO 2 ) emissions, which cause greenhouse effect, decreased by 782.87 g/kWh when rapeseed oil ethyl ester was used and by 782.26 g/kWh when rapeseed oil methyl ester was used instead of fossil diesel fuel. Rapeseed oil ethyl ester was more rapidly biodegradable in aqua environment when compared with rapeseed oil methyl ester and especially with fossil diesel fuel. During a standard 21 day period, 97.7% of rapeseed oil methyl ester, 98% of rapeseed oil ethyl ester and only 61.3% of fossil diesel fuel were biologically decomposed. (author)

The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

Science.gov (United States)

Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

2013-11-01

Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

Directory of Open Access Journals (Sweden)

Bard Jean-Marie

2008-10-01

Full Text Available Abstract Background Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects. Methods In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents or without plant sterols (control for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C. Secondary measurements were changes in total cholesterol (TC, non-HDL cholesterol (non-HDL-C, HDL cholesterol (HDL-C and triglycerides. Results Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p 96%, and products were well tolerated. Conclusion Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

The European source term code ESTER - basic ideas and tools for coupling of ATHLET and ESTER

International Nuclear Information System (INIS)

Schmidt, F.; Schuch, A.; Hinkelmann, M.

1993-04-01

The French software house CISI and IKE of the University of Stuttgart have developed during 1990 and 1991 in the frame of the Shared Cost Action Reactor Safety the informatic structure of the European Source TERm Evaluation System (ESTER). Due to this work tools became available which allow to unify on an European basis both code development and code application in the area of severe core accident research. The behaviour of reactor cores is determined by thermal hydraulic conditions. Therefore for the development of ESTER it was important to investigate how to integrate thermal hydraulic code systems with ESTER applications. This report describes the basic ideas of ESTER and improvements of ESTER tools in view of a possible coupling of the thermal hydraulic code system ATHLET and ESTER. Due to the work performed during this project the ESTER tools became the most modern informatic tools presently available in the area of severe accident research. A sample application is given which demonstrates the use of the new tools. (orig.) [de

Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis.

Science.gov (United States)

Hourcade-Potelleret, F; Laporte, S; Lehnert, V; Delmar, P; Benghozi, Renée; Torriani, U; Koch, R; Mismetti, P

2015-06-01

Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. To assess alternative methods to predict clinical response of CETP inhibitors. Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. 51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cobalt-catalyzed hydrogenation of esters to alcohols: unexpected reactivity trend indicates ester enolate intermediacy.

Science.gov (United States)

Srimani, Dipankar; Mukherjee, Arup; Goldberg, Alexander F G; Leitus, Gregory; Diskin-Posner, Yael; Shimon, Linda J W; Ben David, Yehoshoa; Milstein, David

2015-10-12

The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cholesterol Transport Revisited : A New Turbo Mechanism to Drive Cholesterol Excretion

NARCIS (Netherlands)

de Boer, Jan Freark; Kuipers, Folkert; Groen, Albert K.

A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are

Cholesterol (image)

Science.gov (United States)

Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

Science.gov (United States)

Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

2012-01-01

Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL.

Science.gov (United States)

Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

2013-01-01

Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions.

Formation of a ground-state charge-transfer complex in Polyfluorene//[6,6]-Phenyl-C61 butyric acid methyl ester (PCBM) blend films and its role in the function of polymer/PCBM solar cells

Energy Technology Data Exchange (ETDEWEB)

Benson-Smith, J.J.; Bradley, D.D.C.; Nelson, J. [Department of Physics, Imperial College London, London SW7 2BW (United Kingdom); Goris, L.; Vandewal, K.; Haenen, K.; Manca, J.V.; Vanderzande, D. [Institute for Materials Research, Limburgs Universitair Centrum, Wetenschapspark 1, 3590 Diepenbeek (Belgium)

2007-02-12

Evidence is presented for the formation of a weak ground-state charge-transfer complex in the blend films of poly[9,9-dioctylfluorene-co-N-(4-methoxyphenyl)diphenylamine] polymer (TFMO) and [6,6]-phenyl-C{sub 61} butyric acid methyl ester (PCBM), using photothermal deflection spectroscopy (PDS) and photoluminescence (PL) spectroscopy. Comparison of this polymer blend with other polyfluorene polymer/PCBM blends shows that the appearance of this ground-state charge-transfer complex is correlated to the ionization potential of the polymer, but not to the optical gap of the polymer or the surface morphology of the blend film. Moreover, the polymer/PCBM blend films in which this charge-transfer complex is observed also exhibit efficient photocurrent generation in photovoltaic devices, suggesting that the charge-transfer complex may be involved in charge separation. Possible mechanisms for this charge-transfer state formation are discussed as well as the significance of this finding to the understanding and optimization of polymer blend solar cells. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

Cholesterol Test

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... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

NARCIS (Netherlands)

Beynen, A.C.; Katan, M.B.; Gent, van C.M.

1986-01-01

In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and

Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

Directory of Open Access Journals (Sweden)

Stephanie M Marshall

Full Text Available An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL support TICE, antisense oligonucleotides (ASO were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP, which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg mice, which predominantly excrete cholesterol via TICE, and wild type (WT littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

MILD CHOLESTEROL DEPLETION REDUCES AMYLOID-β PRODUCTION BY IMPAIRING APP TRAFFICKING TO THE CELL SURFACE

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Guardia-Laguarta, Cristina; Coma, Mireia; Pera, Marta; Clarimón, Jordi; Sereno, Lidia; Agulló, José M.; Molina-Porcel, Laura; Gallardo, Eduard; Deng, Amy; Berezovska, Oksana; Hyman, Bradley T.; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

2009-01-01

It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP-PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. PMID:19457132

Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

NARCIS (Netherlands)

Jakulj, L.

2013-01-01

Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

Biogenesis of plasma membrane cholesterol

International Nuclear Information System (INIS)

Lange, Y.

1986-01-01

A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from [ 3 H] acetate moved to the plasma membrane with a half-time of 1 h at 37 0 C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane

Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains

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Di Bari Michele A

2011-08-01

Full Text Available Abstract Objective Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial. Methods To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS. Results Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate. Conclusion Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.

Poly(ester-anhydride):poly(beta-amino ester) micro- and nanospheres: DNA encapsulation and cellular transfection.

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Pfeifer, Blaine A; Burdick, Jason A; Little, Steve R; Langer, Robert

2005-11-04

Poly(ester-anhydride) delivery devices allow flexibility regarding carrier dimensions (micro- versus nanospheres), degradation rate (anhydride versus ester hydrolysis), and surface labeling (through the anhydride functional unit), and were therefore tested for DNA encapsulation and transfection of a macrophage P388D1 cell line. Poly(l-lactic acid-co-sebacic anhydride) and poly(l-lactic acid-co-adipic anhydride) were synthesized through melt condensation, mixed with 25 wt.% poly(beta-amino ester), and formulated with plasmid DNA (encoding firefly luciferase) into micro- and nanospheres using a double emulsion/solvent evaporation technique. The micro- and nanospheres were then characterized (size, morphology, zeta potential, DNA release) and assayed for DNA encapsulation and cellular transfection over a range of poly(ester-anhydride) copolymer ratios. Poly(ester-anhydride):poly(beta-amino ester) composite microspheres (6-12 microm) and nanospheres (449-1031 nm), generated with copolymers containing between 0 and 25% total polyanhydride content, encapsulated plasmid DNA (>or=20% encapsulation efficiency). Within this polyanhydride range, poly(adipic anhydride) copolymers provided DNA encapsulation at an increased anhydride content (10%, microspheres; 10-25%, nanospheres) compared to poly(sebacic anhydride) copolymers (1%, microspheres and nanospheres) with cellular transfection correlating with the observed DNA encapsulation.

The Food Matrix and Sterol Characteristics Affect the Plasma Cholesterol Lowering of Phytosterol/Phytostanol1

Science.gov (United States)

Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S.

2013-01-01

Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c. PMID:24228192

[Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

Science.gov (United States)

Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

2014-10-01

The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.

Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL[S

Science.gov (United States)

Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

2013-01-01

Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions. PMID:23099443

Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

Science.gov (United States)

Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

2012-04-15

A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

Application conditions for ester cured alkaline phenolic resin sand

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Ren-he Huang

2016-07-01

Full Text Available Five organic esters with different curing speeds: propylene carbonate (i.e. high-speed ester A; 1, 4-butyrolactone; glycerol triacetate (i.e. medium-speed ester B; glycerol diacetate; dibasic ester (DBE (i.e. low-speed ester C, were chosen to react with alkaline phenolic resin to analyze the application conditions of ester cured alkaline phenolic resin. The relationships between the curing performances of the resin (including pH value, gel pH value, gel time of resin solution, heat release rate of the curing reaction and tensile strength of the resin sand and the amount of added organic ester and curing temperature were investigated. The results indicated the following: (1 The optimal added amount of organic ester should be 25wt.%-30wt.% of alkaline phenolic resin and it must be above 20wt.%-50 wt.% of the organic ester hydrolysis amount. (2 High-speed ester A (propylene carbonate has a higher curing speed than 1, 4-butyrolactone, and they were both used as high-speed esters. Glycerol diacetate is not a high-speed ester in alkaline phenolic resin although it was used as a high-speed ester in ester cured sodium silicate sand; glycerol diacetate and glycerol triacetate can be used as medium-speed esters in alkaline phenolic resin. (3 High-speed ester A, medium-speed ester B (glycerol triacetate and low-speed ester C (dibasic ester, i.e., DBE should be used below 15 ìC, 35 ìC and 50 ìC, respectively. High-speed ester A or low-speed ester C should not be used alone but mixed with medium-speed ester B to improve the strength of the resin sand. (4 There should be a suitable solid content (generally 45wt.%-65wt.% of resin, alkali content (generally 10wt.%-15wt.% of resin and viscosity of alkaline phenolic resin (generally 50-300 mPa≤s in the preparation of alkaline phenolic resin. Finally, the technique conditions of alkaline phenolic resin preparation and the application principles of organic ester were discussed.

Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

Science.gov (United States)

Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O

2016-01-14

Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

NARCIS (Netherlands)

Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

NARCIS (Netherlands)

Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

2016-01-01

Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

NARCIS (Netherlands)

Weggemans, R.M.; Zock, P.L.; Katan, M.B.

2001-01-01

Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

Cholesterol - what to ask your doctor

Science.gov (United States)

... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

Influence of dietary cholesterol on 26-hydroxycholesterol and the effect of 26-hydroxycholesterol on the intracellular free calcium level

International Nuclear Information System (INIS)

Kou, I.L.

1987-01-01

The purpose of this study was to investigate the factors influencing serum level of 26-hydroxycholesterol after long-term consumption of cholesterol by animals. It is also to examine the effect of this sterol on intracellular free calcium level. Purified 26-hydroxycholesterol was synthesized from kryptogenin by the Clemmemsen and Wolff-Kishner reduction method. 26-Hydroxycholesterol was also used for fatty acid esters syntheses, and to study its influence on membranes. Tritiated 26-hydroxycholesterol which was synthesized by an enzymatic method, was used to monitor the 26-hydroxycholesterol loss during the procedure. The ester form of 26-hydroxycholesterol was also synthesized, and used to investigate its effects on membranes. The HPLC method that was developed for the analysis of 26-hydroxycholesterol levels in animal tissues was accurate, efficient, and reproducible for the determination of 26-hydroxycholesterol in plasma. However, it was not suitable for the analysis of other tissues, due to the overlapping of peaks making quantitation difficult

Common Misconceptions about Cholesterol

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... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

NARCIS (Netherlands)

Vrins, Carlos L. J.

2010-01-01

The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

Rearrangement of beta,gamma-unsaturated esters with thallium trinitrate: synthesis of indans bearing a beta-keto ester moiety

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Silva Jr. Luiz F.

2006-01-01

Full Text Available The rearrangement of beta,gamma-unsaturated esters, such as 2-(3,4-dihydronaphthalen-1-yl-propionic acid ethyl ester, with thallium trinitrate (TTN in acetic acid leads to 3-indan-1-yl-2-methyl-3-oxo-propionic acid ethyl ester in good yield, through a ring contraction reaction. The new indans thus obtained feature a beta-keto ester moiety, which would be useful for further functionalization.

Neutral Lipid Biosynthesis in Engineered Escherichia coli: Jojoba Oil-Like Wax Esters and Fatty Acid Butyl Esters

OpenAIRE

Kalscheuer, Rainer; Stöveken, Tim; Luftmann, Heinrich; Malkus, Ursula; Reichelt, Rudolf; Steinbüchel, Alexander

2006-01-01

Wax esters are esters of long-chain fatty acids and long-chain fatty alcohols which are of considerable commercial importance and are produced on a scale of 3 million tons per year. The oil from the jojoba plant (Simmondsia chinensis) is the main biological source of wax esters. Although it has a multitude of potential applications, the use of jojoba oil is restricted, due to its high price. In this study, we describe the establishment of heterologous wax ester biosynthesis in a recombinant E...

Regioselective Synthesis of Cellulose Ester Homopolymers

Science.gov (United States)

Daiqiang Xu; Kristen Voiges; Thomas Elder; Petra Mischnick; Kevin J. Edgar

2012-01-01

Regioselective synthesis of cellulose esters is extremely difficult due to the small reactivity differences between cellulose hydroxyl groups, small differences in steric demand between acyl moieties of interest, and the difficulty of attaching and detaching many protecting groups in the presence of cellulose ester moieties without removing the ester groups. Yet the...

Covalent immobilization of cholesterol esterase and cholesterol oxidase on polyaniline films for application to cholesterol biosensor

Energy Technology Data Exchange (ETDEWEB)

Singh, Suman [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Solanki, Pratima R. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Pandey, M.K. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India)]. E-mail: bansi@mail.nplindia.ernet.in

2006-05-24

Cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been covalently immobilized on electrochemically prepared polyaniline (PANI) films. These PANI/ChEt/ChOx enzyme films have been characterized using UV-visible, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Electrochemical behavior of these films has been studied using cyclic voltammetry (CV) and amperometric techniques, respectively. The PANI/ChEt/ChOx enzyme films show broad oxidation peak from 0.2 to 0.5 V. These PANI/ChEt/ChOx biosensing electrodes have a response time of about 40 s, linearity from 50 to 500 mg/dl of cholesterol oleate concentration. These PANI/ChEt/ChOx films are thermally stable up to 46 deg. C. This polyaniline based cholesterol biosensor has optimum pH in the range of 6.5-7.5, sensitivity as 7.5 x 10{sup -4} nA/mg dl and a lifetime of about 6 weeks.

Replacement of Retinyl Esters by Polyunsaturated Triacylglycerol Species in Lipid Droplets of Hepatic Stellate Cells during Activation

Science.gov (United States)

Testerink, Nicole; Ajat, Mokrish; Houweling, Martin; Brouwers, Jos F.; Pully, Vishnu V.; van Manen, Henk-Jan; Otto, Cees; Helms, J. Bernd; Vaandrager, Arie B.

2012-01-01

Activation of hepatic stellate cells has been recognized as one of the first steps in liver injury and repair. During activation, hepatic stellate cells transform into myofibroblasts with concomitant loss of their lipid droplets (LDs) and production of excessive extracellular matrix. Here we aimed to obtain more insight in the dynamics and mechanism of LD loss. We have investigated the LD degradation processes in rat hepatic stellate cells in vitro with a combined approach of confocal Raman microspectroscopy and mass spectrometric analysis of lipids (lipidomics). Upon activation of the hepatic stellate cells, LDs reduce in size, but increase in number during the first 7 days, but the total volume of neutral lipids did not decrease. The LDs also migrate to cellular extensions in the first 7 days, before they disappear. In individual hepatic stellate cells. all LDs have a similar Raman spectrum, suggesting a similar lipid profile. However, Raman studies also showed that the retinyl esters are degraded more rapidly than the triacylglycerols upon activation. Lipidomic analyses confirmed that after 7 days in culture hepatic stellate cells have lost most of their retinyl esters, but not their triacylglycerols and cholesterol esters. Furthermore, we specifically observed a large increase in triacylglycerol-species containing polyunsaturated fatty acids, partly caused by an enhanced incorporation of exogenous arachidonic acid. These results reveal that lipid droplet degradation in activated hepatic stellate cells is a highly dynamic and regulated process. The rapid replacement of retinyl esters by polyunsaturated fatty acids in LDs suggests a role for both lipids or their derivatives like eicosanoids during hepatic stellate cell activation. PMID:22536341

Replacement of retinyl esters by polyunsaturated triacylglycerol species in lipid droplets of hepatic stellate cells during activation.

Directory of Open Access Journals (Sweden)

Nicole Testerink

Full Text Available Activation of hepatic stellate cells has been recognized as one of the first steps in liver injury and repair. During activation, hepatic stellate cells transform into myofibroblasts with concomitant loss of their lipid droplets (LDs and production of excessive extracellular matrix. Here we aimed to obtain more insight in the dynamics and mechanism of LD loss. We have investigated the LD degradation processes in rat hepatic stellate cells in vitro with a combined approach of confocal Raman microspectroscopy and mass spectrometric analysis of lipids (lipidomics. Upon activation of the hepatic stellate cells, LDs reduce in size, but increase in number during the first 7 days, but the total volume of neutral lipids did not decrease. The LDs also migrate to cellular extensions in the first 7 days, before they disappear. In individual hepatic stellate cells. all LDs have a similar Raman spectrum, suggesting a similar lipid profile. However, Raman studies also showed that the retinyl esters are degraded more rapidly than the triacylglycerols upon activation. Lipidomic analyses confirmed that after 7 days in culture hepatic stellate cells have lost most of their retinyl esters, but not their triacylglycerols and cholesterol esters. Furthermore, we specifically observed a large increase in triacylglycerol-species containing polyunsaturated fatty acids, partly caused by an enhanced incorporation of exogenous arachidonic acid. These results reveal that lipid droplet degradation in activated hepatic stellate cells is a highly dynamic and regulated process. The rapid replacement of retinyl esters by polyunsaturated fatty acids in LDs suggests a role for both lipids or their derivatives like eicosanoids during hepatic stellate cell activation.

Correlation and prediction of mixing thermodynamic properties of ester-containing systems: Ester + alkane and ester + ester binary systems and the ternary dodecane + ethyl pentanoate + ethyl ethanoate

International Nuclear Information System (INIS)

Pérez, Noelia; Fernández, Luís; Ortega, Juan; Toledo, Francisco J.; Wisniak, Jaime

2012-01-01

Highlights: ► Excess enthalpies and volumes were measured for ester–ester–alkane. ► Mixing behaviour for ester–ester, ester–alkane and ester–ester–alkane are analyzed. ► Correlations with a new polynomial model reproduce well the mixing properties. ► UNIFAC predictions for h E result acceptable excluding the ester–ester mixtures. - Abstract: Excess thermodynamic properties V m E and H m E , have been measured for the ternary mixture dodecane + ethyl pentanoate + ethyl ethanoate and for the corresponding binaries dodecane + ethyl pentanoate, dodecane + ethyl ethanoate, ethyl pentanoate + ethyl ethanoate at 298.15 K. All mixtures show endothermic and expansive effects. Experimental results are correlated with a suitable equation whose final form for the excess ternary quantity M E contains the particular contributions of the three binaries (i–j) and a last term corresponding to the ternary, all of them obtained considering fourth-order interactions. The fit goodness for all mixtures is good and comparable to others equations taken from the literature. In this work the dissolution model for the binaries and ternary is analyzed with a special attention to ester–ester binaries whose behaviour is discussed. The application of the UNIFAC group contribution model to estimate the H m E yields acceptable results for the binaries (with the exception of ester–ester) and for the ternary mixture.

Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

Science.gov (United States)

Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

2017-08-01

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

Science.gov (United States)

Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

2012-05-01

In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection.

Science.gov (United States)

Gong, Xin; Qian, Hongwu; Zhou, Xinhui; Wu, Jianping; Wan, Tao; Cao, Pingping; Huang, Weiyun; Zhao, Xin; Wang, Xudong; Wang, Peiyi; Shi, Yi; Gao, George F; Zhou, Qiang; Yan, Nieng

2016-06-02

Niemann-Pick disease type C (NPC) is associated with mutations in NPC1 and NPC2, whose gene products are key players in the endosomal/lysosomal egress of low-density lipoprotein-derived cholesterol. NPC1 is also the intracellular receptor for Ebola virus (EBOV). Here, we present a 4.4 Å structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of EBOV, both determined by single-particle electron cryomicroscopy. NPC1 contains 13 transmembrane segments (TMs) and three distinct lumenal domains A (also designated NTD), C, and I. TMs 2-13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3-7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling. A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantum confinement-tunable ultrafast charge transfer at the PbS quantum dot and phenyl-C61-butyric acid methyl ester interface

KAUST Repository

El-Ballouli, AlA'A O.; Alarousu, Erkki Antero; Bernardi, Marco; Aly, Shawkat Mohammede; Lagrow, Alec P.; Bakr, Osman; Mohammed, Omar F.

2014-01-01

Quantum dot (QD) solar cells have emerged as promising low-cost alternatives to existing photovoltaic technologies. Here, we investigate charge transfer and separation at PbS QDs and phenyl-C61-butyric acid methyl ester (PCBM) interfaces using a combination of femtosecond broadband transient absorption (TA) spectroscopy and steady-state photoluminescence quenching measurements. We analyzed ultrafast electron injection and charge separation at PbS QD/PCBM interfaces for four different QD sizes and as a function of PCBM concentration. The results reveal that the energy band alignment, tuned by the quantum size effect, is the key element for efficient electron injection and charge separation processes. More specifically, the steady-state and time-resolved data demonstrate that only small-sized PbS QDs with a bandgap larger than 1 eV can transfer electrons to PCBM upon light absorption. We show that these trends result from the formation of a type-II interface band alignment, as a consequence of the size distribution of the QDs. Transient absorption data indicate that electron injection from photoexcited PbS QDs to PCBM occurs within our temporal resolution of 120 fs for QDs with bandgaps that achieve type-II alignment, while virtually all signals observed in smaller bandgap QD samples result from large bandgap outliers in the size distribution. Taken together, our results clearly demonstrate that charge transfer rates at QD interfaces can be tuned by several orders of magnitude by engineering the QD size distribution. The work presented here will advance both the design and the understanding of QD interfaces for solar energy conversion. © 2014 American Chemical Society.

Quantum confinement-tunable ultrafast charge transfer at the PbS quantum dot and phenyl-C61-butyric acid methyl ester interface

KAUST Repository

El-Ballouli, AlA'A O.

2014-05-14

Quantum dot (QD) solar cells have emerged as promising low-cost alternatives to existing photovoltaic technologies. Here, we investigate charge transfer and separation at PbS QDs and phenyl-C61-butyric acid methyl ester (PCBM) interfaces using a combination of femtosecond broadband transient absorption (TA) spectroscopy and steady-state photoluminescence quenching measurements. We analyzed ultrafast electron injection and charge separation at PbS QD/PCBM interfaces for four different QD sizes and as a function of PCBM concentration. The results reveal that the energy band alignment, tuned by the quantum size effect, is the key element for efficient electron injection and charge separation processes. More specifically, the steady-state and time-resolved data demonstrate that only small-sized PbS QDs with a bandgap larger than 1 eV can transfer electrons to PCBM upon light absorption. We show that these trends result from the formation of a type-II interface band alignment, as a consequence of the size distribution of the QDs. Transient absorption data indicate that electron injection from photoexcited PbS QDs to PCBM occurs within our temporal resolution of 120 fs for QDs with bandgaps that achieve type-II alignment, while virtually all signals observed in smaller bandgap QD samples result from large bandgap outliers in the size distribution. Taken together, our results clearly demonstrate that charge transfer rates at QD interfaces can be tuned by several orders of magnitude by engineering the QD size distribution. The work presented here will advance both the design and the understanding of QD interfaces for solar energy conversion. © 2014 American Chemical Society.

Synthesis of 11C labelled methyl esters: transesterification of enol esters versus BF3 catalysed esterification-a comparative study

International Nuclear Information System (INIS)

Ackermann, Uwe; Blanc, Paul; Falzon, Cheryl L.; Issa, William; White, Jonathan; Tochon-Danguy, Henri J.; Sachinidis, John I.; Scott, Andrew M.

2006-01-01

C-11 labelled methyl esters have been synthesized via the transesterification of enol esters in the presence of C-11 methanol and 1,3 dichlorodibutylstannoxane as catalyst. This method leaves functional groups intact and allows access to a wider variety of C-11 labelled methyl esters compared to the BF 3 catalysed ester formation, which uses carboxylic acids and C-11 methanol as starting materials

Neutral lipid biosynthesis in engineered Escherichia coli: jojoba oil-like wax esters and fatty acid butyl esters.

Science.gov (United States)

Kalscheuer, Rainer; Stöveken, Tim; Luftmann, Heinrich; Malkus, Ursula; Reichelt, Rudolf; Steinbüchel, Alexander

2006-02-01

Wax esters are esters of long-chain fatty acids and long-chain fatty alcohols which are of considerable commercial importance and are produced on a scale of 3 million tons per year. The oil from the jojoba plant (Simmondsia chinensis) is the main biological source of wax esters. Although it has a multitude of potential applications, the use of jojoba oil is restricted, due to its high price. In this study, we describe the establishment of heterologous wax ester biosynthesis in a recombinant Escherichia coli strain by coexpression of a fatty alcohol-producing bifunctional acyl-coenzyme A reductase from the jojoba plant and a bacterial wax ester synthase from Acinetobacter baylyi strain ADP1, catalyzing the esterification of fatty alcohols and coenzyme A thioesters of fatty acids. In the presence of oleate, jojoba oil-like wax esters such as palmityl oleate, palmityl palmitoleate, and oleyl oleate were produced, amounting to up to ca. 1% of the cellular dry weight. In addition to wax esters, fatty acid butyl esters were unexpectedly observed in the presence of oleate. The latter could be attributed to solvent residues of 1-butanol present in the medium component, Bacto tryptone. Neutral lipids produced in recombinant E. coli were accumulated as intracytoplasmic inclusions, demonstrating that the formation and structural integrity of bacterial lipid bodies do not require specific structural proteins. This is the first report on substantial biosynthesis and accumulation of neutral lipids in E. coli, which might open new perspectives for the biotechnological production of cheap jojoba oil equivalents from inexpensive resources employing recombinant microorganisms.

Ester Tuiksoo / Ester Tuiksoo ; interv. Piret Tali

Index Scriptorium Estoniae

Tuiksoo, Ester, 1965-

2007-01-01

Juhan Partsi valitsuse (05.04.2004-13.04.2005) ja Andrus Ansipi valitsuse (13.04.2005-) põllumajandusminister Ester Tuiksoo oma lapsepõlvest ja elukutsevalikust, poliitilise karjääri algusest ja erakonna valikust, ministritöö kogemustest, naistest poliitikas

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

Science.gov (United States)

Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

International Nuclear Information System (INIS)

Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

2004-01-01

Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

Directory of Open Access Journals (Sweden)

Zhang CY

2014-10-01

Full Text Available Can Yang Zhang, Di Xiong, Yao Sun, Bin Zhao, Wen Jing Lin, Li Juan Zhang School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China Abstract: A novel amphiphilic triblock pH-sensitive poly(ß-amino ester-g-poly(ethylene glycol methyl ether-cholesterol (PAE-g-MPEG-Chol was designed and synthesized via the Michael-type step polymerization and esterification condensation method. The synthesized copolymer was determined with proton nuclear magnetic resonance and gel permeation chromatography. The grafting percentages of MPEG and cholesterol were determined as 10.93% and 62.02%, calculated from the area of the characteristic peaks, respectively. The amphiphilic copolymer was confirmed to self-assemble into core/shell micelles in aqueous solution at low concentrations. The critical micelle concentrations were 6.92 and 15.14 mg/L at pH of 7.4 and 6.0, respectively, obviously influenced by the changes of pH values. The solubility of pH-responsive PAE segment could be transformed depending on the different values of pH because of protonation–deprotonation of the amino groups, resulting in pH sensitivity of the copolymer. The average particle size of micelles increased from 125 nm to 165 nm with the pH decreasing, and the zeta potential was also significantly changed. Doxorubicin (DOX was entrapped into the polymeric micelles with a high drug loading level. The in vitro DOX release from the micelles was distinctly enhanced with the pH decreasing from 7.4 to 6.0. Toxicity testing proved that the DOX-loaded micelles exhibited high cytotoxicity in HepG2 cells, whereas the copolymer showed low toxicity. The results demonstrated how pH-sensitive PAE-g-MPEG-Chol micelles were proved to be a potential vector in hydrophobic drug delivery for tumor therapy. Keywords: micelle, pH-sensitive, cholesterol, poly(ß-amino ester, drug delivery

Synthesis of Co3O4 Cotton-Like Nanostructures for Cholesterol Biosensor

Directory of Open Access Journals (Sweden)

Sami Elhag

2014-12-01

Full Text Available The use of templates to assist and possess a control over the synthesis of nanomaterials has been an attractive option to achieve this goal. Here we have used sodium dodecyl sulfate (SDS to act as a template for the low temperature synthesis of cobalt oxide (Co3O4 nanostructures. The use of SDS has led to tune the morphology, and the product was in the form of “cotton-like” nanostructures instead of connected nanowires. Moreover, the variation of the amount of the SDS used was found to affect the charge transfer process in the Co3O4. Using Co3O4 synthesized using the SDS for sensing of cholesterol was investigated. The use of the Co3O4 synthesized using the SDS was found to yield an improved cholesterol biosensor compared to Co3O4 synthesized without the SDS. The improvement of the cholesterol sensing properties upon using the SDS as a template was manifested in increasing the sensitivity and the dynamic range of detection. The results achieved in this study indicate the potential of using template assisted synthesis of nanomaterials in improving some properties, e.g., cholesterol sensing.

Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity.

Directory of Open Access Journals (Sweden)

Ioanna Vallianou

Full Text Available Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO.The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001, 54% of Low Density Lipoprotein (LDL-cholesterol (p<0.001 and 34.5% of triglycerides (p<0.001. Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins.Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation.

Camphene, a Plant-Derived Monoterpene, Reduces Plasma Cholesterol and Triglycerides in Hyperlipidemic Rats Independently of HMG-CoA Reductase Activity

Science.gov (United States)

Vallianou, Ioanna; Peroulis, Nikolaos; Pantazis, Panayotis; Hadzopoulou-Cladaras, Margarita

2011-01-01

Background Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO). Methodology/Principal Findings The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. Conclusions Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent

Cholesterol - drug treatment

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

Anticholinesterase activity of fluorochloronitroacetic acid esters

Energy Technology Data Exchange (ETDEWEB)

Ivanov, Yu.Ya.; Brel, V.K. Martynov, I.V.

1984-11-01

Results are presented from pharmacologic and biochemical experiments leading to the conclusion that fluorochloronitroacetic acid esters have anticholinesterase activity. Since the esters caused muscular weakness in mice, experiments were performed on isolated tissue preparation. The biochemical experiments consisted of finding the biomolecular constants of irreversible inhibition of acetylcholinesterase by the esters, using acetylcholinesterase from human erythrocytes, as well as horse serum cholinesterase. The ethyl and n-propyl esters of halogen nitroacetic acid were used in all experiments. It was found that the propyl ester caused an increase in the force of individual contractions in the isolated muscle specimens, plus an inability of the muscle to retain tetanus. The substances were determined to have an anticholinesterase effect. The mechanism of cholinesterase inhibition is not yet known. It is probable that the substances acylate the serine hydroxyl of the esterase center of the cholinestersase. 7 references, 1 figure.

Optimization and modeling for the synthesis of sterol esters from deodorizer distillate by lipase-catalyzed esterification.

Science.gov (United States)

Zhang, Xinyu; Yu, Jiang; Zeng, Aiwu

2017-03-01

In this paper, cotton seed oil deodorizer distillate (CSODD), was recovered to obtain fatty acid sterol ester (FASE), which is one of the biological activated substances added as human therapeutic to lower cholesterol. Esterification reactions were carried out using Candida rugosa lipase as a catalyst, and the conversion of phytosterol was optimized using response surface methodology. The highest conversion (90.8 ± 0.4%) was reached at 0.84 wt% enzyme load, 1:25 solvent/CSODD mass ratio, and 44.2 °C after 12 H reaction. A kinetic model based on the reaction rate equation was developed to describe the reaction process. The activation energy of the reaction was calculated to be 56.9 kJ/mol and the derived kinetic parameters provided indispensable basics for further study. The optimization and kinetic research of synthesizing FASE from deodorizer distillate provided necessary information for the industrial applications in the near future. Experimental results showed that the proposed process is a promising alternative to recycle sterol esters from vegetable oil deodorizer distillates in a mild, efficient, and environmental friendly method. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Cholesterol autoxidation in phospholipid membrane bilayers

International Nuclear Information System (INIS)

Sevanian, A.; McLeod, L.L.

1987-01-01

Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

Science.gov (United States)

Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

2017-12-01

Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

QSAR for cholinesterase inhibition by organophosphorus esters and CNDO/2 calculations for organophosphorus ester hydrolysis

Science.gov (United States)

Johnson, H.; Kenley, R. A.; Rynard, C.; Golub, M. A.

1985-01-01

Quantitative structure-activity relationships were derived for acetyl- and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of catonic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR'P(O)X, where R and R' are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO-derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrogen hydrolysis rate constant.

Remnant cholesterol and ischemic heart disease

DEFF Research Database (Denmark)

Varbo, Anette; Nordestgaard, Børge G

2014-01-01

PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

Differential Polymer Structure Tunes Mechanism of Cellular Uptake and Transfection Routes of Poly(β-amino ester) Polyplexes in Human Breast Cancer Cells

OpenAIRE

Kim, Jayoung; Sunshine, Joel C.; Green, Jordan J.

2013-01-01

Successful gene delivery with non-viral particles has several barriers, including cellular uptake, endosomal escape, and nuclear transport. Understanding the mechanisms behind these steps is critical to enhancing the effectiveness of gene delivery. Polyplexes formed with poly(β-amino ester)s (PBAEs) have been shown to effectively transfer DNA to various cell types, but the mechanism of their cellular uptake has not been identified. This is the first study to evaluate the uptake mechanism of P...

Method of making a cyanate ester foam

Science.gov (United States)

Celina, Mathias C.; Giron, Nicholas Henry

2014-08-05

A cyanate ester resin mixture with at least one cyanate ester resin, an isocyanate foaming resin, other co-curatives such as polyol or epoxy compounds, a surfactant, and a catalyst/water can react to form a foaming resin that can be cured at a temperature greater than 50.degree. C. to form a cyanate ester foam. The cyanate ester foam can be heated to a temperature greater than 400.degree. C. in a non-oxidative atmosphere to provide a carbonaceous char foam.

Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial.

Science.gov (United States)

Nicholls, Stephen J; Ray, Kausik K; Ballantyne, Christie M; Beacham, Lauren A; Miller, Debra L; Ruotolo, Giacomo; Nissen, Steven E; Riesmeyer, Jeffrey S

2017-06-01

The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured. Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, pstatin dose (pstatin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02). While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux.

Science.gov (United States)

Chen, Liang; Yao, Qiying; Xu, Siwei; Wang, Hongyan; Qu, Peng

2018-01-01

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the development of atherosclerosis. The activated NLRP3 inflammasome has been reported to promote macrophage foam cell formation, but not all studies have obtained the same result, and how NLRP3 inflammasome is involved in the formation of foam cells remains elusive. We used selective NLRP3 inflammasome inhibitors and NLRP3-deficient THP-1 cells to assess the effect of NLRP3 inflammasome inhibition on macrophage foam cell formation, oxidized low-density lipoprotein (ox-LDL) uptake, esterification, and cholesterol efflux, as well as the expression of associated proteins. Inhibition of the NLRP3 inflammasome attenuated foam cell formation, diminished ox-LDL uptake, and promoted cholesterol efflux from THP-1 macrophages. Moreover, it downregulated CD36, acyl coenzyme A: cholesterol acyltransferase-1 and neutral cholesterol ester hydrolase expression; upregulated ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression; but had no effect on the expression of scavenger receptor class A and ATP-binding cassette transporter G1. Collectively, our findings show that inhibition of the NLRP3 inflammasome decreases foam cell formation of THP-1 macrophages via suppression of ox-LDL uptake and enhancement of cholesterol efflux, which may be due to downregulation of CD36 expression and upregulation of ABCA1 and SR-BI expression, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms of foam cell formation in atherosclerosis.

Science.gov (United States)

Chistiakov, Dimitry A; Melnichenko, Alexandra A; Myasoedova, Veronika A; Grechko, Andrey V; Orekhov, Alexander N

2017-11-01

Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

Science.gov (United States)

Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

2014-01-01

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

Bile acid sequestrants for cholesterol

Science.gov (United States)

... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

Atheroprotective potentials of curcuminoids against ginger extract in hypercholesterolaemic rabbits.

Science.gov (United States)

Elseweidy, M M; Younis, N N; Elswefy, S E; Abdallah, F R; El-Dahmy, S I; Elnagar, G; Kassem, H M

2015-01-01

The anti-atherogenic potentials of total ginger (Zingiber officinale) extract (TGE) or curcuminoids extracted from turmeric (Curcuma longa), members of family Zingiberaceae, were compared in hypercholesterolaemia. Rabbits were fed either normal or atherogenic diet. The rabbits on atherogenic diet received treatments with TGE or curcumenoids and placebo concurrently for 6 weeks (n = 6). The anti-atherogenic effects of curcuminoids and ginger are mediated via multiple mechanisms. This effect was correlated with their ability to lower cholesteryl ester transfer protein activity. Ginger extract exerted preferential effects on plasma lipids, reverse cholesterol transport, cholesterol synthesis and inflammatory status. Curcuminoids, however, showed superior antioxidant activity.

to HDL-cholesterol functionality

Directory of Open Access Journals (Sweden)

Malara Marzena

2016-05-01

Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

Science.gov (United States)

Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

2017-01-01

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

NARCIS (Netherlands)

Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

NARCIS (Netherlands)

Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

2007-01-01

BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

Science.gov (United States)

Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

2011-06-01

Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

Science.gov (United States)

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

2017-05-01

Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

Allied, MGC link on cyanate esters

International Nuclear Information System (INIS)

Wood, A.

1993-01-01

In the latest of a line of joint ventures in its plastics business, Allied Signal has reached agreement with Mitsubishi Gas Chemical (MGC) to jointly develop thermoset cyanate ester resins and blends. The deal will involve further development of Allied Signal's Primaset phenol-formaldehyde cyanate ester resins, a new entrant in the thermoset arena. Although the Primaset resins were discovered in the 1960s, this would be the first time they are available commercially. The deal will marry Primaset technology with MGC's Skylex bisphenol A cyanate ester resins, says Fred DiAntonis, director/advanced materials at Allied Signal. The two firms are looking at marketing blends of the two materials. The potential market for these resins, used commercially by the electronics industry in printed circuit boards and by the aerospace industry in composites, is significant, says Robert P. Viarengo, Allied Signal president/performance materials. By aligning ourselves with MGC, the world leader in cyanate ester resin, we anticipate moving forward aggressively. The main competitor is Ciba, which acquired bisphenol A cyanate ester resins with its purchase of Rhone-Poulenc's high temperature resins business. DiAntonis estimates the market for cyanate ester resins could be worth $150 million by the end of the decade, although development costs have been in the tens of millions of dollars range

Impact of unhealthy lifestyle behaviors and obesity on cholesteryl ester transfer protein among adolescent males.

Science.gov (United States)

Hirschler, Valeria; Meroño, Tomas; Maccallini, Gustavo; Gomez Rosso, Leonardo; Aranda, Claudio; Brites, Fernando

2011-01-01

Cholesteryl ester transfer protein (CETP) has been proposed to be associated with high risk of cardiovascular disease. Increased CETP activity was previously reported in obese adults, although its association with lifestyle behaviors has not been assessed in healthy adolescents. We undertook this study to determine the association between CETP activity and overweight/obesity, insulin resistance markers, components of the metabolic syndrome and lifestyle behaviors in healthy adolescent males. Data were collected from 164 adolescents from an amateur rugby club. Body mass index (BMI), blood pressure (BP), Tanner stages, lipids, glucose, insulin and CETP activity were measured. Questionnaires for daily intake of breakfast, sweet drinks, milk, and hours of TV watching were completed. About 26% of the adolescents were obese and 23% overweight. The prevalence of metabolic syndrome was 6.7%. CETP activity was higher in obese than in normal and overweight adolescents (174 ± 35, 141 ± 30, and 149 ± 38%/ml/min, respectively; p 2 h/day (r = 0.17; p 0.02), and milk intake >3 glasses/day (r = 0.16; p = 0.03). Multivariate analysis showed that triglycerides, LDL-C, HDL-C, TV watching >2 h/day, milk intake >3 glasses/day and BMI were significant independent predictors for CETP (R(2) = 0.41). Unhealthy lifestyle habits such as TV watching >2 h daily and milk intake higher than three glasses per day and the increase in BMI were shown to be closely associated with high CETP activity in apparently healthy adolescent males. Future longitudinal studies should be performed to confirm these findings. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

Trapping crystal nucleation of cholesterol monohydrate

DEFF Research Database (Denmark)

Solomonov, I.; Weygand, M.J.; Kjær, K.

2005-01-01

Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers......, at least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

Science.gov (United States)

Lopez, Adam M; Jones, Ryan Dale; Repa, Joyce J; Turley, Stephen D

2018-06-07

Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7 wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared to their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma ALT and AST activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency.

Synthesis of a new energetic nitrate ester

Energy Technology Data Exchange (ETDEWEB)

Chavez, David E [Los Alamos National Laboratory

2008-01-01

Nitrate esters have been known as useful energetic materials since the discovery of nitroglycerin by Ascanio Sobrero in 1846. The development of methods to increase the safety and utility of nitroglycerin by Alfred Nobel led to the revolutionary improvement in the utility of nitroglycerin in explosive applications in the form of dynamite. Since then, many nitrate esters have been prepared and incorporated into military applications such as double-based propellants, detonators and as energetic plasticizers. Nitrate esters have also been shown to have vasodilatory effects in humans and thus have been studied and used for treatments of ailments such as angina. The mechanism of the biological response towards nitrate esters has been elucidated recently. Interestingly, many of the nitrate esters used for military purposes are liquids (ethylene glycol dinitrate, propylene glycol dinitrate, etc). Pentaerythritol tetranitrate (PETN) is one of the only solid nitrate esters, besides nitrocellulose, that is used in any application. Unfortunately, PETN melting point is above 100 {sup o}C, and thus must be pressed as a solid for detonator applications. A more practical material would be a melt-castable explosive, for potential simplification of manufacturing processes. Herein we describe the synthesis of a new energetic nitrate ester (1) that is a solid at ambient temperatures, has a melting point of 85-86 {sup o}C and has the highest density of any known nitrate ester composed only of carbon, hydrogen, nitrogen and oxygen. We also describe the chemical, thermal and sensitivity properties of 1 as well as some preliminary explosive performance data.

A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: Evaluation of the diabetes-accelerated atherosclerosis risk

Energy Technology Data Exchange (ETDEWEB)

Huang Qilin; An Yarui; Tang Linlin; Jiang Xiaoli; Chen Hua; Bi Wenji [Department of Chemistry, East China Normal University, Shanghai 200062 (China); Wang Zhongchuan [Department of Anorectal Surgery, Xinhua Hospital, Affiliated to School of Medicine of Shanghai Jiaotong University, Shanghai 200092 (China); Zhang Wen, E-mail: wzhang@chem.ecnu.edu.cn [Department of Chemistry, East China Normal University, Shanghai 200062 (China)

2011-11-30

Graphical abstract: In this paper, we reported a novel dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the diabetes-accelerated atherosclerosis risk. The biosensor was firstly modified with a poly-thionine (PTH) film as electron transfer mediator (ETM), then the gold nanoparticles (GNPs) were covered on the surface of PTH to act as tiny conduction centers for facilitating the electron transfer between enzymes and electrode. The schematic of the dual biosensor is shown in figure. The developed dual biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibited a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 {mu}M, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 {mu}M. The results of the diabetic mice demonstrated that the cholesterol level was not changed obviously with the increase of glucose level in serum, while the cholesterol level was enhanced together with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, the hallmark of early atherosclerosis. These findings indicated the possibility that high glucose induced by diabetes might increase the macrophage cholesterol level to further accelerate atherosclerosis development. Highlights: Black-Right-Pointing-Pointer A novel biosensor was developed to determine glucose and cholesterol simultaneously. Black-Right-Pointing-Pointer The dual enzymatic-biosensor has good selectivity and high sensitivity. Black-Right-Pointing-Pointer We determined glucose and cholesterol in the real samples of diabetic mice. Black-Right-Pointing-Pointer The results showed that high glucose might increase the macrophage cholesterol level. Black-Right-Pointing-Pointer It provided useful experimental

A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: Evaluation of the diabetes-accelerated atherosclerosis risk

International Nuclear Information System (INIS)

Huang Qilin; An Yarui; Tang Linlin; Jiang Xiaoli; Chen Hua; Bi Wenji; Wang Zhongchuan; Zhang Wen

2011-01-01

Graphical abstract: In this paper, we reported a novel dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the diabetes-accelerated atherosclerosis risk. The biosensor was firstly modified with a poly-thionine (PTH) film as electron transfer mediator (ETM), then the gold nanoparticles (GNPs) were covered on the surface of PTH to act as tiny conduction centers for facilitating the electron transfer between enzymes and electrode. The schematic of the dual biosensor is shown in figure. The developed dual biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibited a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 μM, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 μM. The results of the diabetic mice demonstrated that the cholesterol level was not changed obviously with the increase of glucose level in serum, while the cholesterol level was enhanced together with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, the hallmark of early atherosclerosis. These findings indicated the possibility that high glucose induced by diabetes might increase the macrophage cholesterol level to further accelerate atherosclerosis development. Highlights: ► A novel biosensor was developed to determine glucose and cholesterol simultaneously. ► The dual enzymatic-biosensor has good selectivity and high sensitivity. ► We determined glucose and cholesterol in the real samples of diabetic mice. ► The results showed that high glucose might increase the macrophage cholesterol level. ► It provided useful experimental evidences for diabetes-accelerate atherosclerosis. - Abstract: In this paper, a novel dual enzymatic-biosensor is described for

Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

Science.gov (United States)

Li, Yong; Chen, Youliang; Li, Hua

2017-01-01

Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield. Copyright © 2016 Elsevier B.V. All rights reserved.

Cholesterol Medicines: MedlinePlus Health Topic

Science.gov (United States)

... heart diseases . There are two main types of cholesterol. LDL is the "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in ... 75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher You ...

pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol-b-PEG-b-(PAE-g-cholesterol for anticancer drug delivery and controlled release

Directory of Open Access Journals (Sweden)

Huang X

2017-03-01

Full Text Available Xiangxuan Huang,1 Wenbo Liao,1 Gang Zhang,1 Shimin Kang,1 Can Yang Zhang2 1School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, USA Abstract: A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters-g-cholesterol-b-poly(ethylene glycol-b-(poly(β-amino esters-g-cholesterol ((PAE-g-Chol-b-PEG-b-(PAE-g-Chol was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 µg/mL, 12.6 µg/mL, 17.4 µg/mL, and 26.6 µg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The pKb of the polymer was confirmed to be approximately 6.5 by the acid–base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20% and entrapment efficiency (60% using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the

Fundamental Characterization of the Micellar Self-Assembly of Sophorolipid Esters.

Science.gov (United States)

Koh, Amanda; Todd, Katherine; Sherbourne, Ezekiel; Gross, Richard A

2017-06-13

Surfactants are ubiquitous constituents of commercial and biological systems that function based on complex structure-dependent interactions. Sophorolipid (SL) n-alkyl esters (SL-esters) comprise a group of modified naturally derived glycolipids from Candida bombicola. Herein, micellar self-assembly behavior as a function of SL-ester chain length was studied. Surface tensions as low as 31.2 mN/m and critical micelle concentrations (CMCs) as low as 1.1 μM were attained for diacetylated SL-decyl ester (dASL-DE) and SL-octyl ester, respectively. For deacetylated SL-esters, CMC values reach a lower limit at SL-ester chains above n-butyl (SL-BE, 1-3 μM). This behavior of SL-esters with increasing hydrophobic tail length is unlike other known surfactants. Diffusion-ordered spectroscopy (DOSY) and T 1 relaxation NMR experiments indicate this behavior is due to a change in intramolecular interactions, which impedes the self-assembly of SL-esters with chain lengths above SL-BE. This hypothesis is supported by micellar thermodynamics where a disruption in trends occurs at n-alkyl ester chain lengths above those of SL-BE and SL-hexyl ester (SL-HE). Diacetylated (dA) SL-esters exhibit an even more unusual trend in that CMC increases from 1.75 to 815 μM for SL-ester chain lengths of dASL-BE and dASL-DE, respectively. Foaming studies, performed to reveal the macroscopic implications of SL-ester micellar behavior, show that the observed instability in foams formed using SL-esters are due to coalescence, which highlights the importance of understanding intermicellar interactions. This work reveals that SL-esters are an important new family of green high-performing surfactants with unique structure-property relationships that can be tuned to optimize micellar characteristics.

Transintestinal cholesterol excretion in humans

NARCIS (Netherlands)

Reeskamp, Laurens F.; Meessen, Emma C. E.; Groen, Albert K.

2018-01-01

Purpose of review To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. Recent findings TICE is the net effect of cholesterol excretion by

Technetium and rhenium tracers with metabolizable ester functions

International Nuclear Information System (INIS)

Syhre, R.; Seifert, S.; Schneider, F.; Pietzsch, H.J.; Spies, H.; Johannsen, B.

1993-01-01

Re-DMSA (dimercaptosuccinic acid) ester complexes were prepored by ligand exchange reactions. To determine whether the ester band in Re-DMSA ester complexes is susceptible to cleavage by esterases, incubation experiments with tissue homogenates and plasma were carried out. (BBR)

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

Science.gov (United States)

Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

2018-03-01

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

Science.gov (United States)

Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

2017-08-01

Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

21 CFR 172.854 - Polyglycerol esters of fatty acids.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyglycerol esters of fatty acids. 172.854 Section... HUMAN CONSUMPTION Multipurpose Additives § 172.854 Polyglycerol esters of fatty acids. Polyglycerol esters of fatty acids, up to and including the decaglycerol esters, may be safely used in food in...

Stability of a metabolizable ester bond in radioimmunoconjugates

International Nuclear Information System (INIS)

Arano, Yasushi; Wakisaka, Kouji; Mukai, Takahiro; Uezono, Takashi; Motonari, Hiroshi; Akizawa, Hiromichi; Kairiyama, Claudia; Ohmomo, Yoshiro; Tanaka, Chiaki; Ishiyama, Munetaka; Sakahara, Harumi; Konishi, Junji; Yokoyama, Akira

1996-01-01

Ester bonds have been used as metabolizable linkages to reduce radioactivity levels in non-target tissues following the administration of antibodies labeled with metallic radionuclides. In this radiochemical design of antibodies, while the ester bonds should be cleaved rapidly in non-target tissues, high stability of the ester bonds in plasma is also required to preserve target radioactivity levels. To assess the structural requirements to stabilize the ester bond, a new benzyl-EDTA-derived bifunctional chelating agent with an ester bond, (1-[4-[4-(2-maleimidoethoxy)succinamido]benzyl]ethylenediamine-N,N,N',N'- tetraacetic acid; MESS-Bz-EDTA), was developed. MESS-Bz-EDTA was coupled with a thiolated monoclonal antibody (OST7, IgG 1 ) prepared by reducing its disulfide bonds to introduce the ester bond close and proximal to the antibody molecule. For comparison, 1-[4-(5-maleimidopentyl)aminobenzyl]ethylenediamine-N,N,N',N'-tetraacetic acid (EMCS-Bz-EDTA) and meleimidoethyl 3-[ 131 I]iodohippurate (MIH) was coupled to OST7 under the same conjunction chemistry. When incubated in 50% murine plasma or a buffered-solution of neutral pH, OST7-MESS-Bz-EDTA- 111 In rapidly released the radioactivity, and more than 95% of the initial radioactivity was liberated after a 24 h incubation in both solutions, due to a cleavage of the ester bond. On the other hand, only about 20% of the radioactivity was released from OST7-MIH- 131 I in both solutions during the same incubation period. In mice biodistribution studies, while a slightly faster radioactivity clearance from the blood with less radioactivity levels in the liver and kidneys was observed with OST7-MIH- 131 I than with OST7-EMCS-Bz-EDTA- 111 In, OST7-MESS-Bz-EDTA- 111 In indicated radioactivity clearance from the blood much faster than and almost comparable to that of OST7-MIH- 131 I and succinamidobenzyl-EDTA- 111 In, respectively. These findings as well as previous findings on radiolabeled antibodies with ester bonds

LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

Science.gov (United States)

Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina

2015-08-01

Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

Cholesterol and related sterols autoxidation.

Science.gov (United States)

Zerbinati, Chiara; Iuliano, Luigi

2017-10-01

Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

Chemical constituents from bark of Cenostigma macrophyllum: cholesterol occurrence; Constituintes quimicos das cascas do caule de Cenostigma macrophyllum: ocorrencia de colesterol

Energy Technology Data Exchange (ETDEWEB)

Silva, Hilris Rocha e; Silva, Carmem Cicera Maria da; Caland Neto, Laurentino Batista; Lopes, Jose Arimateia Dantas; Cito, Antonia Maria das Gracas Lopes; Chaves, Mariana H. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Quimica]. E-mail: mariana@ufpi.br

2007-07-01

Phytochemical investigation of the bark of Cenostigma macrophyllum (Leguminosae-Caesapinioideae) resulted in the isolation and identification of valoneic acid dilactone, ellagic acid, lupeol, alkyl ferulate, four free sterols (cholesterol, campesterol, stigmasterol and sitosterol), a mixture of sitosteryl ester derivatives of fatty acids, sitosterol-3-O-beta-D-glucopyranoside, stigmasterol-3-O-beta-D-glucopyranoside and saturated and unsaturated fatty acids. The structures of the isolated compounds were identified by {sup 1}H and {sup 13}C NMR spectral analysis and comparison with literature data. The mixtures of 3-beta-hydroxysterols and fatty acids were analysed by GC/MS. (author)

High Cholesterol in Children and Teens

Science.gov (United States)

... dairy products. The body needs some cholesterol to work properly. But if your child or teen has high cholesterol (too much cholesterol in the blood), he or she has a higher risk of coronary artery disease and other heart diseases. What causes high cholesterol in children and teens? Three main ...

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

Science.gov (United States)

Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

2016-08-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

Science.gov (United States)

Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

2016-01-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

Directory of Open Access Journals (Sweden)

Maria João Nunes

Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

Plasma glucose, cholesterol, triglyceride, and glycerol concentrations in the postmature rabbit.

Science.gov (United States)

Harlow, A C; Roux, J F; Shapiro, M I

1980-02-15

Plasma cholesterol, triglycerides, glycerol, and glucose concentrations were measured in term and postmature rabbits. The data show that the term and postmature mothers have significantly higher glycemia than their fetuses. However, triglyceride and cholesterol concentrations are lower in the postmature mother than in her fetus. Postmature fetuses are characterized by very high plasma triglyceride and cholesterol concentrations. The results demonstrate that postmaturity is accompanied by maternal and fetal lipid metabolic changes related to a decrease in the transfer of maternal fatty acids through the placenta and to a diminution in fetal liver glucose utilization. The postmature fetus is then in a relative state of fasting and must rely on its own supply of fuel (glycogen and lipids) to provide cells for growth and survival. The maternal metabolic changes can possibly be explained by a decreased utilization of maternal substrates by the fetus, the placenta becoming insufficient. The close interrelationship of fetal and maternal lipid metabolism with the activity of the placenta suggests that an accurate knowledge of the metabolic changes taking place in the fetus during alteration of the maternal environment is indispensable to the understanding of the short- and long-term effects of maternal disease on the fetus.

Estereótipos e mulheres na cultura marroquina

OpenAIRE

Sadiqi,Fatima

2008-01-01

Estereótipos sobre as mulheres no Marrocos podem ser caracterizados como crenças culturais incompletas e inexatas mantidas por algumas pessoas e que se encontram inscritos em expressões lingüísticas ou em discursos subliminares. A cultura popular marroquina emprega representações poderosas para transmitir e sustentar tais estereótipos. Embora existam alguns estereótipos positivos, a maioria dos estereótipos sobre as mulheres no Marrocos é negativa e reflete ditames patriarcais subliminares qu...

Methyl esters from vegetable oils with hydroxy fatty acids: Comparison of lesquerella and castor methyl esters

Science.gov (United States)

The search for alternative feedstocks for biodiesel as partial replacement for petrodiesel has recently extended to castor oil. In this work, the castor oil methyl esters were prepared and their properties determined in comparison to the methyl esters of lesquerella oil, which in turn is seen as alt...

Environmentally friendly properties of vegetable oil methyl esters

Directory of Open Access Journals (Sweden)

Gateau Paul

2005-07-01

Full Text Available Measurements were carried out on Vegetable Oil Methyl Esters (VOME or FAME answering the most recent specifications. The products tested are RME (Rapeseed oil Methyl Ester, ERME (Erucic Rapeseed oil Methyl Esters, SME (Sunflower oil Methyl Esters, and HOSME (High Oleic Sunflower oil Methyl Esters. They contain more than 99.5% of fatty acid mono esters. The compositions are given. VOME are not volatile and they are not easily flammable. They are not soluble in water and they are biodegradable. According to the methods implemented for the determination of the German classification of substances hazardous to waters WGK, they are not toxic on mammals and unlike diesel fuel they are not toxic on fish, daphnia, algae and bacteria. The RME is not either toxic for shrimps. According to tests on rabbits, RME and SME are not irritating for the skin and the eyes. VOME display particularly attractive environmental properties.

Controlling Cholesterol with Statins

Science.gov (United States)

... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Directory of Open Access Journals (Sweden)

Frans Stellaard

2017-01-01

Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

Preparation of Spirocyclic β-Proline Esters

DEFF Research Database (Denmark)

Fjelbye, Kasper; Marigo, Mauro; Clausen, Rasmus Prætorius

2017-01-01

A series of novel N-Bn-protected spirocyclic β-proline esters were prepared using [3+2] cycloaddition and subsequently converted into their corresponding aldehydes. In addition, two novel N-Cbz-protected spirocyclic β-proline esters were prepared using intramolecular cyclization starting from...

Nanoscale Membrane Domain Formation Driven by Cholesterol

DEFF Research Database (Denmark)

Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

2017-01-01

Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

Energy Technology Data Exchange (ETDEWEB)

Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

2013-09-15

The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

International Nuclear Information System (INIS)

Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S.

2013-01-01

The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 °C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5–700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 °C

No Evidence for Spontaneous Lipid Transfer at ER-PM Membrane Contact Sites.

Science.gov (United States)

Merklinger, Elisa; Schloetel, Jan-Gero; Spitta, Luis; Thiele, Christoph; Lang, Thorsten

2016-04-01

Non-vesicular lipid transport steps play a crucial role in lipid trafficking and potentially include spontaneous exchange. Since membrane contact facilitates this lipid transfer, it is most likely to occur at membrane contact sites (MCS). However, to date it is unknown whether closely attached biological membranes exchange lipids spontaneously. We have set up a system for studying the exchange of lipids at MCS formed between the endoplasmic reticulum (ER) and the plasma membrane. Contact sites were stably anchored and the lipids cholesterol and phosphatidylcholine (PC) were not capable of transferring spontaneously into the opposed bilayer. We conclude that physical contact between two associated biological membranes is not sufficient for transfer of the lipids PC and cholesterol.

The Endoplasmic Reticulum Coat Protein II Transport Machinery Coordinates Cellular Lipid Secretion and Cholesterol Biosynthesis*

Science.gov (United States)

Fryer, Lee G. D.; Jones, Bethan; Duncan, Emma J.; Hutchison, Claire E.; Ozkan, Tozen; Williams, Paul A.; Alder, Olivia; Nieuwdorp, Max; Townley, Anna K.; Mensenkamp, Arjen R.; Stephens, David J.; Dallinga-Thie, Geesje M.; Shoulders, Carol C.

2014-01-01

Triglycerides and cholesterol are essential for life in most organisms. Triglycerides serve as the principal energy storage depot and, where vascular systems exist, as a means of energy transport. Cholesterol is essential for the functional integrity of all cellular membrane systems. The endoplasmic reticulum is the site of secretory lipoprotein production and de novo cholesterol synthesis, yet little is known about how these activities are coordinated with each other or with the activity of the COPII machinery, which transports endoplasmic reticulum cargo to the Golgi. The Sar1B component of this machinery is mutated in chylomicron retention disorder, indicating that this Sar1 isoform secures delivery of dietary lipids into the circulation. However, it is not known why some patients with chylomicron retention disorder develop hepatic steatosis, despite impaired intestinal fat malabsorption, and why very severe hypocholesterolemia develops in this condition. Here, we show that Sar1B also promotes hepatic apolipoprotein (apo) B lipoprotein secretion and that this promoting activity is coordinated with the processes regulating apoB expression and the transfer of triglycerides/cholesterol moieties onto this large lipid transport protein. We also show that although Sar1A antagonizes the lipoprotein secretion-promoting activity of Sar1B, both isoforms modulate the expression of genes encoding cholesterol biosynthetic enzymes and the synthesis of cholesterol de novo. These results not only establish that Sar1B promotes the secretion of hepatic lipids but also adds regulation of cholesterol synthesis to Sar1B's repertoire of transport functions. PMID:24338480

Intracellular transport of cholesterol in mammalian cells

International Nuclear Information System (INIS)

Brasaemle, D.L.

1989-01-01

The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of [ 3 H]cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth

Supercooled smectic nanoparticles

DEFF Research Database (Denmark)

Kuntsche, Judith; Westesen, K; Drechsler, M

2004-01-01

The possibility of preparing nanoparticles in the supercooled thermotropic liquid crystalline state from cholesterol esters with saturated acyl chains as well as the incorporation of model drugs into the dispersions was investigated using cholesteryl myristate (CM) as a model cholesterol ester....

Synthesis of Estolide 2-ethylhexyl Ester from Ricinus communis

International Nuclear Information System (INIS)

Nazrizawati Ahmad Tajuddin; Nor Habibah Rosli

2013-01-01

Estolide 2-ethylhexyl ester synthesized through condensation reaction between ricinoleic acid from castor oil (Ricinus communis) and lauric acid, and then capped with 2-ethylhexyl alcohol. The reaction was continuously conducted under vacuum for 24 hours. Product of 2-ethylhexyl ester was characterized by using Fourier Transform Infrared (FTIR) to determine functional group and Nuclear Magnetic Resonans (NMR) for structure's determination. The presence of ester group at 1738.23 cm -1 wavenumber indicates that the formation of estolide ester has occurred. The vibration peak of C-O at 1174.60 cm -1 and 1117.10 cm -1 support the formation of ester. The presence of CH 2 bending indicated the long-chain compound. The ester methine signal at 3.8669 ppm indicated the estolide linkage in the 1 H-NMR spectrum while the 13 C-NMR showed two carbonyl signals at 173.41 ppm for acid and 173.56 ppm for ester. (author)

Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

International Nuclear Information System (INIS)

AlRowaily, Meshref A

2008-01-01

The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

Phthalate esters in marine algae

OpenAIRE

Gezgin, Tuncay; Güven, Kasim Cemal; Akçin, Göksel

2001-01-01

Abstract o-Phthalate esters as diethyl phthalate, dibutyl phthalate, di-isobutyl phthalate and diethylhexyl phthalate were identified at surface and inner part of algae collected in the Bosphorus, as Ulva lactuca, Enteromorpha linza, Cystoseria barbata, Pterocladia capillaceaeand Ceramium rubrum. The same esters were also detected in seawater samples taken from the same area. Thus parallelism in pollution was noted between the algae and the surrounding seawater,

Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1.

Science.gov (United States)

Ishikawa-Sasaki, Kumiko; Nagashima, Shigeo; Taniguchi, Koki; Sasaki, Jun

2018-04-15

Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A, and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIβ (PI4KB) at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB-dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we demonstrate AiV hijacking of the cellular cholesterol transport system involving oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein. AiV RNA replication was inhibited by silencing cellular proteins known to be components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP-A/B), the PI4P-phosphatase SAC1, and PI-transfer protein β. OSBP, VAP-A/B, and SAC1 were present at RNA replication sites. We also found various previously unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3, OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein interaction-based OSBP recruitment has not been reported for other picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP-mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA replication. Electron microscopy showed that AiV-induced vesicle-like structures were close to ER membranes. Altogether, we conclude that AiV directly recruits the cholesterol transport machinery through protein-protein interactions, resulting in formation of membrane contact sites between the ER and AiV ROs and cholesterol supply to the ROs. IMPORTANCE Positive-strand RNA viruses utilize host pathways to modulate the lipid composition of

Cholesterol in unusual places

Energy Technology Data Exchange (ETDEWEB)

Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

2010-11-01

Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

Cholesterol in unusual places

International Nuclear Information System (INIS)

Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

2010-01-01

Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

[Cholesterol reducing food certainly is useful].

Science.gov (United States)

Stalenhoef, A F

1997-12-27

The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

Extraction and Liquid Chromatography-Tandem Mass Spectrometry Detection of 3-Monochloropropanediol Esters and Glycidyl Esters in Infant Formula.

Science.gov (United States)

Leigh, Jessica K; MacMahon, Shaun

2016-12-14

A method was developed for the extraction of fatty acid esters of 3-chloro-1,2-propanediol (3-MCPD) and glycidol from infant formula, followed by quantitative analysis of the extracts using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These process-induced chemical contaminants are found in refined vegetable oils, and studies have shown that they are potentially carcinogenic and/or genotoxic, making their presence in edible oils (and processed foods containing these oils) a potential health risk. The extraction procedure involves a liquid-liquid extraction, where powdered infant formula is dissolved in water and extracted with ethyl acetate. Following shaking, centrifugation, and drying of the organic phase, the resulting fat extract is cleaned-up using solid-phase extraction and analyzed by LC-MS/MS. Method performance was confirmed by verifying the percent recovery of each 3-MCPD and glycidyl ester in a homemade powdered infant formula reference material. Average ester recoveries in the reference material ranged from 84.9 to 109.0% (0.6-9.5% RSD). The method was also validated by fortifying three varieties of commercial infant formulas with a 3-MCPD and glycidyl ester solution. Average recoveries of the esters across all concentrations and varieties of infant formula ranged from 88.7 to 107.5% (1.0-9.5% RSD). Based on the validation results, this method is suitable for producing 3-MCPD and glycidyl ester occurrence data in all commercially available varieties of infant formula.

Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?

Science.gov (United States)

La Marca, Valeria; Maresca, Bernardetta; Spagnuolo, Maria Stefania; Cigliano, Luisa; Dal Piaz, Fabrizio; Di Iorio, Giuseppe; Abrescia, Paolo

2016-04-01

24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

Science.gov (United States)

Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

2013-02-15

Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

[New agents for hypercholesterolemia].

Science.gov (United States)

Pintó, Xavier; García Gómez, María Carmen

2016-02-19

An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.