Abstract：
:The ability to exogenously present cell-surface receptors in high-affinity conformations in a synthetic system offers an opportunity to provide host cells with protection from pathogenic toxins. This strategy requires improvement of the synthetic receptor binding affinity against its native counterpart, particularly with polyvalent toxins where clustering of membrane receptors can hinder binding. Here we demonstrate that reconstituted lipoprotein, nanometer-sized discoidal lipid bilayers bounded by apolipoprotein and functionalized by incorporation of pathogen receptors, provides a means to enhance toxin-receptor binding through molecular-level control over the receptor microenvironment (specifically, its rigidity, composition, and heterogeneity). Using a Foerster Resonance Energy Transfer (FRET)-based assay, we found that reconstituted lipoprotein incorporating low concentrations of ganglioside monosialotetrahexosylganglioside (GM1) binds polymeric cholera toxin with significantly higher affinity than liposomes or supported lipid bilayers, most likely a result of the enhanced control over receptor clustering provided by the lipoprotein platform. Using wide-area epifluorescence, we found that this enhanced binding capacity can be effectively utilized to divert cholera toxin away from populations of healthy mammalian cells. In summary, we found that reconstitutions of high-density lipoprotein can be engineered to include specific pathogen receptors; that their pathogen binding affinity is altered, presumably due to attenuation of receptor aggregation; and that these assemblies are effective at protecting cells from biological toxins.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Bricarello DA,Mills EJ,Petrlova J,Voss JC,Parikh ANdoi
10.1194/jlr.M007401subject
Has Abstractpub_date
2010-09-01 00:00:00pages
2731-8issue
9eissn
0022-2275issn
1539-7262pii
jlr.M007401journal_volume
51pub_type
杂志文章abstract：:Delta-6 desaturase (D6D) catalyzes the first step in the synthesis of highly unsaturated fatty acids (HUFA) such as arachidonic (AA), docosapentaenoic (DPAn-6), and docosahexaenoic (DHA) acids, as well as the last desaturation of DPAn-6 and DHA. We created D6D-null mice (-/-), which enabled us to study HUFA deficiency...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M900039-JLR200
更新日期：2009-09-01 00:00:00
abstract：:Human monocyte-derived macrophages secrete lipoprotein lipase (LPL) in culture. The regulation of human macrophage LPL production is poorly understood. Since bacterial lipopolysaccharide (LPS) alters production of several macrophage secretory products, its effect on human monocyte-derived macrophage LPL was tested. LP...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:The sphingomyelin pathway is an important signal transduction system regulating various cellular functions. However, little is known about the effect of sphingomyelin metabolites on vasomotor function. We examined the vascular effects of sphingomyelin, sphingosine, and sphingomyelinase (SPMase) in vitro. In pig corona...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is present in the blood plasma and acts as a pivotal intercellular signal transmitter in the immune system by recruiting lymphocytes from the thymus and secondary lymphoid tissues. The plasma S1P concentration is maintained by the supply of S1P from erythrocytes. Previously, we showed tha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D071068
更新日期：2016-11-01 00:00:00
abstract：:The role of phosphodiesterase in glucagon resistance of large adipocytes was investigated. A comparison was made of phosphodiesterase activities of homogenates prepared from isolated small (mean diameter approximately 45 micro m) and large (mean diameter approximately 78 micro m) adipocytes, using various concentratio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-01-01 00:00:00
abstract：:Essential fatty acids (EFA) are important structural and functional components of cell membranes. Their deficiency has been associated with several clinical and biochemical abnormalities. In the present study, the lipid profile as well as the concentration, composition, and metabolism of lipoproteins were examined in ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Arterial wall lipid retention is believed to be due primarily to ionic interactions between lipoproteins and proteoglycans. Thus, oxidized low density lipoproteins (LDL), with decreased positive charge relative to native LDL, should have decreased interaction with negatively charged proteoglycans. However, oxidized LD...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Mice bearing the Ehrlich ascites tumor were fed diets rich in either coconut oil or sunflower oil. From 20 to 40% less lipid was present in the ascites tumor fluid when the mice were fed the sunflower oil diet. This was associated with a reduction in the amount of very low density lipoproteins (VLDL) and high density ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-05-01 00:00:00
abstract：:Glycosylphosphatidylinositol (GPI) enriches GPI-anchored proteins (GPI-AP) in lipid rafts by intimate interaction of its lipid moiety with sphingolipids and cholesterol. In addition to such lipid-lipid interactions, it has been reported that GPI may interact with protein moiety linked to GPI and affect protein conform...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034421
更新日期：2013-04-01 00:00:00
abstract：:The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liv...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M007948
更新日期：2010-11-01 00:00:00
abstract：:Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25-50 mug/ml inhibited staurosporine-induced apoptosis in THP-1 cells...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700100-JLR200
更新日期：2008-01-01 00:00:00
abstract：:The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800058-JLR200
更新日期：2008-07-01 00:00:00
abstract：:The effect of fatty acids on secretion of triglyceride-rich lipoprotein (d less than 1.006 g/ml) by CaCo-2 cells was studied. Of the fatty acids studied, oleic acid (18:1) was the most potent stimulator of newly synthesized triglyceride secretion in triglyceride-rich lipoproteins followed in descending order by 18:2, ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:The relative rates of hydrolysis of the secondary ester in glycerol 1,3-benzylidene 2-oleate and in glycerol 1,3-dihexadecyl ether 2-oleate, and of the primary and secondary esters in triolein were determined. Both unaltered and selectively inactivated rat pancreatic juice were used as sources of enzyme. It was found ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-01-01 00:00:00
abstract：:A novel and rapid method for the detergent-mediated synthesis of protein-lipid complexes has been developed and has several advantages over detergent dialysis methods. This new method involves co-incubation of human apolipoprotein A-I (apoA-I), the major protein component of high density lipoproteins (HDL), and dipalm...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:The extent to which the heart can convert alpha-linolenic acid (alpha-LNA, 18:3n-3) to longer chain n-3 PUFAs is not known. Conversion rates can be measured in vivo using radiolabeled alpha-LNA and a kinetic fatty acid model. [1-(14)C]alpha-LNA was infused intravenously for 5 min in unanesthetized rats that had been f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800093-JLR200
更新日期：2008-08-01 00:00:00
abstract：:Long-chain polyunsaturated fatty acids (PUFA) orchestrate immunity and inflammation through their capacity to be converted to potent inflammatory mediators. We assessed associations of FADS gene cluster polymorphisms and fasting serum PUFA concentrations in a fully ascertained, geographically isolated founder populati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M008359
更新日期：2010-09-01 00:00:00
abstract：:Rab GTPases require special machinery for protein prenylation, which include Rab escort protein (REP) and Rab geranylgeranyl transferase (RGGT). The current model of Rab geranylgeranylation proposes that REP binds Rab and presents it to RGGT. After geranylgeranylation of Rab C-terminal cysteines, REP delivers the pren...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R500017-JLR200
更新日期：2006-03-01 00:00:00
abstract：:Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by ads...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P016816
更新日期：2011-12-01 00:00:00
abstract：:Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increas...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500203-JLR200
更新日期：2006-02-01 00:00:00
abstract：:The objective of this study was to establish a new lipoprotein lipase (LPL) and hepatic lipase (HL) activity assay method. Seventy normal volunteers were recruited. Lipase activities were assayed by measuring the increase in absorbance at 546 nm due to the quinoneine dye. Reaction mixture-1 (R-1) contained dioleoylgly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700528-JLR200
更新日期：2008-07-01 00:00:00
abstract：:Lipoprotein metabolism can be studied by the analysis of lipoprotein production in cell culture. An inherent problem in such an analysis is the low concentration of lipoproteins in culture supernatants. The difficulty comes from the fact that the samples must be concentrated prior to any analysis. The concentrating me...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:C26 Bile of the 24-nor-5beta-cholestane series were prepared starting from methyl cholate. A Grignard reaction of methyl magnesium iodide with methyl cholate yielded 24-nor-5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol which was dehydrated TO FORM a mixture of 24-nor-5beta-cholest-23-ene-3alpha, 7alpha, 12 alpha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:Lipidomics, the mass spectrometry-based comprehensive analysis of lipids, has attracted attention as an analytical approach to provide novel insight into lipid metabolism and to search for biomarkers. However, an ideal method for both comprehensive and quantitative analysis of lipids has not been fully developed. Here...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D083014
更新日期：2018-07-01 00:00:00
abstract：:Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins wer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
abstract：:Quantitatively and rapidly analyzing lipids is necessary to elucidate their biological functions. Herein, we developed a quantitative method for various lipid classes using supercritical fluid chromatography (SFC) coupled with a charged aerosol detector (CAD), providing high-throughput data analysis to detect a large ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D094516
更新日期：2019-08-01 00:00:00
abstract：:Previously, we identified the low density lipoprotein receptor (LDLR) promoter region -17 to -1 as a novel sterol-independent regulatory element (SIRE) that mediates the stimulating effect of oncostatin M (OM). The goal of this study was to identify the OM-induced transcription activator that binds to the SIRE sequenc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200126-jlr200
更新日期：2002-09-01 00:00:00
abstract：:Triglyceride-rich lipoproteins derived from ten normo- and hyperlipidemic apoE-2 homozygotes were analyzed for their composition, beta-VLDL content, and their ability to induce cholesteryl ester storage in macrophages. In six of these probands apoE sequence analysis revealed that the cysteine residues were at position...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
abstract：:3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) are metabolized into chenodeoxycholic acid and cholic acid, respectively, through oxidation and cleavage of the terminal three carbons of the side chain. The present study was desig...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-02-01 00:00:00
