Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.
AuthorsGillard BK, Rosales C, Pillai BK, Lin HY, Courtney HS, Pownall HJ,
JournalBiochemistry
PubMed ID20879789
Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ~400000 HDL particles and ... More
Human granulosa cells use high density lipoprotein cholesterol for steroidogenesis.
AuthorsAzhar S, Tsai L, Medicherla S, Chandrasekher Y, Giudice L, Reaven E
JournalJ Clin Endocrinol Metab
PubMed ID9506760
This study examines the ability of human high density lipoproteins (HDL3) to deliver cholesteryl esters to human granulosa cells and describes the selective cholesterol pathway by which this occurs. Luteinized cells obtained from subjects undergoing in vitro fertilization-embryo transfer procedures were incubated with native HDL3 (or radiolabeled or fluorescently labeled ... More
High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion.
AuthorsSilver DL, Wang N, Xiao X, Tall AR
JournalJ Biol Chem
PubMed ID11301333
'High density lipoprotein (HDL) mediates reverse transport of cholesterol from atheroma foam cells to the liver, but the mechanisms of hepatic uptake and trafficking of HDL particles are poorly understood. In contrast to its accepted role as a cell surface receptor, scavenger receptor class B type 1 (SR-BI) is shown ... More
Intracellular localization and metabolism of chylomicron remnants in the livers of low density lipoprotein receptor-deficient mice and apoE-deficient mice. Evidence for slow metabolism via an alternative apoE-dependent pathway.
'The metabolism of chylomicron remnants in mice deficient in low density lipoprotein receptor (LDLr) or apolipoprotein E (apoE) was compared with that of control C57BL/6J mice. Mice were injected intravenously with chylomicron-like emulsions labeled with radioactive lipids. Blood samples were taken at fixed time intervals from the retro-orbital sinus, and ... More
Direct visualization of lipid deposition and reverse lipid transport in a perfused artery : roles of VLDL and HDL.
AuthorsRutledge JC, Mullick AE, Gardner G, Goldberg IJ
JournalCirc Res
PubMed ID10764410
'The major goal of this study was to determine the interactions of VLDL surface and core lipids with the artery wall. We first demonstrated in vitro that surface lipid in VLDL could be traced using the phospholipid-like fluorescent probe 1,1''-dioctadecyl-3,3, 3'',3''-tetramethyl-indocarbocyanine (DiI). The core of VLDL particles was traced by ... More
Ceramide triggers budding of exosome vesicles into multivesicular endosomes.
'Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal ... More
Kinetics and inhibition of lipid exchange catalyzed by plasma cholesteryl ester transfer protein (lipid transfer protein).
AuthorsEpps DE, Greenlee KA, Harris JS, Thomas EW, Castle CK, Fisher JF, Hozak RR, Marschke CK, Melchior GW, Kézdy FJ
JournalBiochemistry
PubMed ID7548004
'The cholesteryl ester transfer protein-catalyzed cholesteryl ester transfer is inhibited by two compounds identified by a large-scale screening of cholesterol backbone-containing molecules. Kinetic analysis shows that U-95,594, an amino steroid, inhibits competitively the cholesteryl ester transfer protein-catalyzed transfer of both cholesteryl esters and triglycerides, as well from high-density lipoproteins as ... More
Expression of scavenger receptor class B type 1 (SR-BI) promotes microvillar channel formation and selective cholesteryl ester transport in a heterologous reconstituted system.
AuthorsReaven E, Leers-Sucheta S, Nomoto A, Azhar S
JournalProc Natl Acad Sci U S A
PubMed ID11171999
'In the "selective" cholesteryl ester (CE) uptake process, surface-associated lipoproteins [high density lipoprotein (HDL) and low density lipoprotein] are trapped in the space formed between closely apposed surface microvilli (microvillar channels) in hormone-stimulated steroidogenic cells. This is the same location where an HDL receptor (SR-BI) is found. In the current ... More
D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains.
AuthorsMakino A, Ishii K, Murate M, Hayakawa T, Suzuki Y, Suzuki M, Ito K, Fujisawa T, Matsuo H, Ishitsuka R, Kobayashi T
JournalBiochemistry
PubMed ID16584188
'D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is a frequently used inhibitor of glycosphingolipid biosynthesis. However, some interesting characteristics of D-PDMP cannot be explained by the inhibition of glycolipid synthesis alone. In the present study, we showed that d-PDMP inhibits the activation of lysosomal acid lipase by late endosome/lysosome specific lipid, bis(monoacylglycero)phosphate (also called as ... More
Lateral diffusion of small compounds in human stratum corneum and model lipid bilayer systems.
AuthorsJohnson ME, Berk DA, Blankschtein D, Golan DE, Jain RK, Langer RS
JournalBiophys J
PubMed ID8913603
'An image-based technique of fluorescence recovery after photobleaching (video-FRAP) was used to measure the lateral diffusion coefficients of a series of nine fluorescent probes in two model lipid bilayer systems, dimyristoylphosphatidylcholine (DMPC) and DMPC/cholesterol (40 mol%), as well as in human stratum corneum-extracted lipids. The probes were all lipophilic, varied ... More
Human arterial proteoglycans increase the rate of proteolytic fusion of low density lipoprotein particles.
'Low density lipoprotein (LDL) particles can undergo fusion in the arterial intima, where they are bound to proteoglycans. Here we studied the effect of human arterial proteoglycans on proteolytic fusion of LDL in vitro. For this purpose, an assay was devised based on fluorescence resonance energy transfer that allowed continuous ... More
AuthorsSchmeck C, Gielen-Haertwig H, Vakalopoulos A, Bischoff H, Li V, Wirtz G, Weber O,
JournalBioorg Med Chem Lett
PubMed ID20137927
In the course of our efforts to identify orally active cholesteryl ester transfer protein (CETP) inhibitors, we have continued to explore tetrahydrochinoline derivatives. Based on BAY 19-4789 structural modifications led to the discovery of novel cycloalkyl substituted compounds. Thus, example 11b is a highly potent CETP inhibitor both in vitro ... More
In vivo evaluation of pH-sensitive polymer-based immunoliposomes targeting the CD33 antigen.
AuthorsSimard P, Leroux JC,
JournalMol Pharm
PubMed ID20476756
The purpose of this study was to evaluate in vivo a targeted pH-sensitive liposomal formulation tailored to promote the efficient intracellular delivery of 1-beta-d-arabinofuranosylcytosine (ara-C) to human myeloid leukemia cells. Specifically, pH-sensitive immunoliposomes were obtained by anchoring a copolymer of dioctadecyl, N-isopropylacrylamide and methacrylic acid in bilayers of PEGylated liposomes ... More
Method for measuring the activities of cholesteryl ester transfer protein (lipid transfer protein).
AuthorsEpps DE, Harris JS, Greenlee KA, Fisher JF, Marschke CK, Castle CK, Ulrich RG, Moll TS, Melchior GW, Kézdy FJ
JournalChem Phys Lipids
PubMed ID7586092
A continuous recording fluorescence assay was developed for cholesteryl ester transfer protein (CETP). The assay measures the increase in fluorescence accompanying the relocation of fluorescent lipids, cholesteryl esters and triglycerides, from a donor emulsion to an acceptor emulsion. In the absence of CETP, the quantum yields of the fluorescent lipids ... More
Use of fluorescent cholesteryl ester microemulsions in cholesteryl ester transfer protein assays.
AuthorsBisgaier CL, Minton LL, Essenburg AD, White A, Homan R
JournalJ Lipid Res
PubMed ID8228645
In the present report we describe a simple and practical method to assess CETP activity in a defined system by use of microemulsions containing a fluorescent cholesteryl ester analog. The microemulsions are stable, simple to prepare, and can be made to defined composition. Initial transfer rates are easily determined by ... More
A synthetic mimic of the secretory granule for drug delivery.
AuthorsKiser PF, Wilson G, Needham D
JournalNature
PubMed ID9697768
Secretory cells contain submicroscopic granules composed of a polyanionic polymer network that is collapsed owing to the presence of hydronium ions and weak base cations. The network is encapsulated within a lipid membrane, and functions as a vehicle for the osmotically inert storage of a variety of granule-bound endogenous mediator ... More
Sterol structure determines the separation of phases and the curvature of the liquid-ordered phase in model membranes.
AuthorsBacia K, Schwille P, Kurzchalia T
JournalProc Natl Acad Sci U S A
PubMed ID15722414
The existence of lipid rafts in biological membranes in vivo is still debated. In contrast, the formation of domains in model systems has been well documented. In giant unilamellar vesicles (GUVs) prepared from ternary mixtures of dioleoyl-phosphatidylcholine/sphingomyelin/cholesterol, a clear separation of liquid-disordered and sphingomyelin-enriched, liquid-ordered phases could be observed. This ... More
Cholesterol uptake by the 'selective' pathway of ovarian granulosa cells: early intracellular events.
AuthorsReaven E, Tsai L, Azhar S
JournalJ Lipid Res
PubMed ID7595083
Although the 'selective' pathway is a major cholesteryl ester (CE) uptake pathway used by steroidogenic cells, essentially nothing is known about the itinerary of the CE once it is extracted from lipoproteins at the cell surface. In the current report we have begun to trace 'selective' pathway internalized-CE using both ... More
Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.
Type 2 diabetes (T2D) is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db) mice are given cholesteryl ester intraperitoneally (IP), peritoneal macrophages (PerMPhis) recovered from these animals showed a 58% ... More
Saturated fat-rich diet enhances selective uptake of LDL cholesteryl esters in the arterial wall.
AuthorsSeo T, Qi K, Chang C, Liu Y, Worgall TS, Ramakrishnan R, Deckelbaum RJ
JournalJ Clin Invest
PubMed ID16041409
Plasma LDL levels and atherosclerosis both increase on a saturated fat-rich (SAT) diet. LDL cholesterol delivery to tissue may occur via uptake of the LDL particles or via selective uptake (SU), wherein cholesteryl ester (CE) enters cells without concomitant whole-particle uptake. It is not known how dietary fats might directly ... More
Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle.
AuthorsJennings LJ, Xu QW, Firth TA, Nelson MT, Mawe GM
JournalAm J Physiol
PubMed ID10564108
Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with ... More
Cholesteryl ester transfer protein inhibition by PD 140195.
AuthorsBisgaier CL, Essenburg AD, Minton LL, Homan R, Blankley CJ, White A
JournalLipids
PubMed ID7854005
The presence of plasma cholesteryl ester transfer protein (CETP) activity may be atherogenic, and, therefore, strategies to inhibit its activity or production may result in a beneficial effect on lipoprotein profiles and the disease process. The current report describes 4-phenyl-5-tridecyl-4H-1,2,4- triazole-3-thiol (PD 140195), a novel CETP inhibitor. The concentration-dependent inhibition ... More
Uptake and cellular localization of exogenous lipids by Giardia lamblia, a primitive eukaryote.
AuthorsStevens TL, Gibson GR, Adam R, Maier J, Allison-Ennis M, Das S
JournalExp Parasitol
PubMed ID9207743
Giardia lamblia trophozoites are unable to carry out de novo lipid synthesis. It is therefore likely that lipids are acquired from the small intestine of the host, in which the trophozoites are exposed to free and conjugated fatty acids, various sterols, phospholipids, bile acids, and bile-lipid mixed micelles. Here we ... More
Immunotargeting of liposomes to activated vascular endothelial cells: a strategy for site-selective delivery in the cardiovascular system.
AuthorsSpragg DD, Alford DR, Greferath R, Larsen CE, Lee KD, Gurtner GC, Cybulsky MI, Tosi PF, Nicolau C, Gimbrone MA
JournalProc Natl Acad Sci U S A
PubMed ID9238057
Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activation in vivo and inducible in cultured human umbilical ... More
Potentials of liposomes in diagnosis and treatment of pulmonary metastases: an experimental study in the rat.
AuthorsRoveda L, Prati U, Diomede L, Salmona M, Bottiroli G, Scoppetta N, Nazari S
JournalEur J Cardiothorac Surg
PubMed ID8855432
OBJECTIVE: The ultimate goal of the therapy of lung metastases is to destroy all malignant cells while sparing normal ones. Liposomes represent a novel approach for the selective transport of tracers and therapeutic agents to cancer cells because of their flexibility, low toxicity, wide range of possible variants, simplicity to ... More
Mapping cholesteryl ester analogue uptake and intracellular flow in Paramecium by confocal fluorescence microscopy.
AuthorsRamoino P, Fronte P, Fato M, Beltrame F, Diaspro A
JournalJ Microsc
PubMed ID12460448
In Paramecium primaurelia the uptake and intracellular flow of cholesteryl ester was studied by fluorescence confocal laser scanning optical microscopy and by the fluorescent analogue cholesteryl-BODIPY FL C12 (BODIPY-CE). The BODIPY FL fluorophore has the characteristic of emitting green fluorescence, which is red-shifted as the probe concentrates. In cells incubated ... More
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells.
AuthorsLakkaraju A, Finnemann SC, Rodriguez-Boulan E
JournalProc Natl Acad Sci U S A
PubMed ID17578916
Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the ... More
VIP receptors as molecular targets of breast cancer: implications for targeted imaging and drug delivery.
AuthorsDagar S, Sekosan M, Lee BS, Rubinstein I, Onyüksel H
JournalJ Control Release
PubMed ID11489489
Receptors for vasoactive intestinal peptide (VIP-R) are overexpressed in human breast cancer. This phenomenon may have important diagnostic and therapeutic implications because carrier systems loaded with imaging or therapeutic agents, and with surface ligands to VIP-R could potentially be actively targeted to breast cancer. Previously, we have prepared sterically stabilized ... More
Intracellular events in the "selective" transport of lipoprotein-derived cholesteryl esters.
AuthorsReaven E, Tsai L, Azhar S
JournalJ Biol Chem
PubMed ID8663101
The current study utilizes human, apoE-free high density lipoprotein reconstituted with a highly specific fluorescent-cholesteryl ester probe to define the initial steps and regulatory sites associated with the "selective" uptake and intracellular itinerary of lipoprotein-derived cholesteryl esters. Bt2cAMP-stimulated ovarian granulosa cells were used as the experimental model, and both morphological ... More
Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.
Authors
JournalNat Nanotechnol
PubMed ID32313216
SR-BI mediates neutral lipid sorting from LDL to lipid droplets and facilitates their formation.
Authors
JournalPLoS One
PubMed ID33057430
SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation.