ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation.

Abstract:

:ABCA1 exports cholesterol and phospholipids from cells by a multistep pathway that involves forming cell surface lipid domains, solubilizing these lipids by apolipoproteins, binding of apolipoproteins to ABCA1, and activating signaling processes. Here we used a mutational analysis approach to evaluate the relationship between these events. We prepared seven naturally occurring mutants and one artificial missense mutant of ABCA1 with varying degrees of impaired function, expressed them to similar levels as wild-type ABCA1 on the cell surface of BHK cells, and measured ABCA1-dependent lipid export, apolipoprotein A-I (apoA-I) binding, and signaling activities. Linear regression analyses showed that cholesterol and phospholipid efflux and cellular apoA-I binding correlated significantly with the ability of ABCA1 to form cell surface lipid domains. Lipid export and cellular apoA-I binding activities and formation of lipid domains also correlated with the amount of apoA-I that could be cross-linked to ABCA1. Moreover, each of these lipid export and apoA-I binding activities correlated with apoA-I-induced Janus kinase 2 (JAK2) activation. Thus, these missense mutations in ABCA1 impair lipid export, apoA-I binding, and apoA-I-stimulated JAK2 activities to similar extents, indicating that these processes are highly interactive components of a pathway that functions to export lipids from cells.

journal_name

J Lipid Res

authors

Vaughan AM,Tang C,Oram JF

doi

10.1194/jlr.M800366-JLR200

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

285-92

issue

2

eissn

0022-2275

issn

1539-7262

pii

M800366-JLR200

journal_volume

50

pub_type

杂志文章
  • Comprehensive analysis of the major lipid classes in sebum by rapid resolution high-performance liquid chromatography and electrospray mass spectrometry.

    abstract::Sebum is a complex lipid mixture that is synthesized in sebaceous glands and excreted on the skin surface. The purpose of this study was the comprehensive detection of the intact lipids that compose sebum. These lipids exist as a broad range of chemical structures and concentrations. Sebum was collected with SebuTape(...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.D008391

    authors: Camera E,Ludovici M,Galante M,Sinagra JL,Picardo M

    更新日期:2010-11-01 00:00:00

  • Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver.

    abstract::Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Skottova N,Savonen R,Lookene A,Hultin M,Olivecrona G

    更新日期:1995-06-01 00:00:00

  • Vitamin A transport in chicken plasma: isolation and characterization of retinol-binding protein (RBP), prealbumin (PA), and RBP--PA complex.

    abstract::Vitamin A-transporting protein in chicken plasma was purified by column chromatography on DEAE-Sephadex and Sephadex G-100; the protein formed a complex of retinol-binding protein (RBP) with prealbumin (PA). The molecular weight of the 1:1 molar complex was estimated to be 76,000 by gel filtration, and the sedimentati...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Abe T,Muto Y,Hosoya N

    更新日期:1975-05-01 00:00:00

  • A 13CO2 breath test to assess the metabolism of triglyceride-rich lipoprotein remnants in mice.

    abstract::Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath wa...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Martins IJ,Redgrave TG

    更新日期:1998-03-01 00:00:00

  • Apolipoprotein-defined lipoprotein subclasses, serum apolipoproteins, and carotid intima-media thickness in T1D.

    abstract::Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and apolipoproteins predict vascular events in the general and type 2 diabetes populations, but data in T1D are limited. We examined associations of ADLS, serum apolipoproteins, and conventional lipids with carotid intima-media thickness (IMT) measured c...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.P080143

    authors: Basu A,Jenkins AJ,Stoner JA,Zhang Y,Klein RL,Lopes-Virella MF,Garvey WT,Schade DS,Wood J,Alaupovic P,Lyons TJ,Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications Research Group.

    更新日期:2018-05-01 00:00:00

  • A novel semiautomated method for the estimation of free fatty acid in serum or plasma.

    abstract::A modification of the semiautomated assay method of Antonis (1965. J. Lipid Res. 6:307-312) for free fatty acid is presented. Free fatty acids are extracted from serum or plasma into di-n-butyl ether-2-methoxyethanol; the extract is almost free from phospholipids. The acids are analyzed in a portion of extract by a co...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Bowyer DE,Cridland JS,King JP

    更新日期:1978-02-01 00:00:00

  • Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome.

    abstract::Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the m...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.P085050

    authors: Dushianthan A,Cusack R,Grocott MPW,Postle AD

    更新日期:2018-06-01 00:00:00

  • Long-chain acyl-CoA synthetase 4 modulates prostaglandin E₂ release from human arterial smooth muscle cells.

    abstract::Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. Purified ACSL4 is an arachidonic acid (20:4)-preferring ACSL isoform, and ACSL4 is therefore a probable regulator of lipid mediator production in intact cells. Eicosanoids play important roles in ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M013292

    authors: Golej DL,Askari B,Kramer F,Barnhart S,Vivekanandan-Giri A,Pennathur S,Bornfeldt KE

    更新日期:2011-04-01 00:00:00

  • Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion.

    abstract::Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cho...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M054882

    authors: Wang Y,Gusarova V,Banfi S,Gromada J,Cohen JC,Hobbs HH

    更新日期:2015-07-01 00:00:00

  • Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease.

    abstract::This paper describes the purification and some of the properties of an enzyme from human spleen that catalyzes the hydrolysis of sphingomyelin with the formation of ceramide and phosphoryl choline. The enzyme, which is located in the subcellular particulate fraction that sediments between 700 and 8500 g, is readily ma...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Schneider PB,Kennedy EP

    更新日期:1967-05-01 00:00:00

  • Apolipoprotein B-100 production and cholesteryl ester content in the liver of developing chick.

    abstract::In the chick, the large cholesteryl ester (CE) store present in the liver during the last period of embryonic life increases at hatching and is rapidly depleted after 2-7 days of postnatal life. In this study we asked whether these changes were associated with variations in the hepatic production of apoB-containing li...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Tarugi P,Nicolini S,Marchi L,Ballarini G,Calandra S

    更新日期:1994-11-01 00:00:00

  • Thematic review series: skin lipids. Antimicrobial lipids at the skin surface.

    abstract::The skin surface represents our interface with the external environment, and as such, is our first line of defense against microbial colonization and infection. Lipids at the skin surface are thought to underlie at least part of an antimicrobial barrier. Some of these lipids are synthesized in the epidermis and are ca...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:10.1194/jlr.R700016-JLR200

    authors: Drake DR,Brogden KA,Dawson DV,Wertz PW

    更新日期:2008-01-01 00:00:00

  • The role of oxysterols in control of endothelial stiffness.

    abstract::Endothelial dysfunction is a key step in atherosclerosis development. Our recent studies suggested that oxLDL-induced increase in endothelial stiffness plays a major role in dyslipidemia-induced endothelial dysfunction. In this study, we identify oxysterols, as the major component of oxLDL, responsible for the increas...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M027102

    authors: Shentu TP,Singh DK,Oh MJ,Sun S,Sadaat L,Makino A,Mazzone T,Subbaiah PV,Cho M,Levitan I

    更新日期:2012-07-01 00:00:00

  • ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differentiation and foam cell formation.

    abstract::The zinc finger protein ZNF202 is a transcriptional repressor that binds to promoter elements predominantly found in genes involved in lipid metabolism. Here we demonstrate that ZNF202 mRNA expression is inversely correlated with ATP binding cassette A1 (ABCA1), ABCG1, and apolipoprotein E (apoE) in human monocytes. U...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M300016-JLR200

    authors: Langmann T,Schumacher C,Morham SG,Honer C,Heimerl S,Moehle C,Schmitz G

    更新日期:2003-05-01 00:00:00

  • A method for determination of saturated phosphatidylcholine.

    abstract::Phosphatidylcholine preparations containing saturated and unsaturated molecular species were subjected to KMnO(4)-NaIO(4) oxidation in aqueous acetic acid, which left only disaturated species intact. After the oxidation, the remaining intact phosphatidylcholine was separated by thin-layer chromatography. The procedure...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Shimojo T,Abe M,Ota M

    更新日期:1974-09-01 00:00:00

  • Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis.

    abstract::Small angle X-ray diffraction was used to examine arterial smooth muscle cell (SMC) plasma membranes isolated from control and cholesterol-fed (2%) atherosclerotic rabbits. A microsomal membrane enriched with plasma membrane obtained from animals fed cholesterol for up to 13 weeks showed a progressive elevation in the...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Tulenko TN,Chen M,Mason PE,Mason RP

    更新日期:1998-05-01 00:00:00

  • Saturated fatty acids enhance osteoclast survival.

    abstract::Hyperlipidemia and marrow fat are associated with lowering bone density in vivo, suggesting that lipid contributes to bone loss. Using bone marrow-derived macrophages, we investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was signifi...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800626

    authors: Oh SR,Sul OJ,Kim YY,Kim HJ,Yu R,Suh JH,Choi HS

    更新日期:2010-05-01 00:00:00

  • Insulin binding and insulin response of adipocytes from rats adapted to fat feeding.

    abstract::The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ip C,Tepperman HM,Holohan P,Tepperman J

    更新日期:1976-11-01 00:00:00

  • Expression and characterization of a C24 bile acid 7 alpha-dehydratase from Eubacterium sp. strain VPI 12708 in Escherichia coli.

    abstract::The intestinal bacterium Eubacterium sp. strain VPI 12708 has been shown to have a bile acid 7 alpha/7 beta-dehydroxylation pathway. A large bile acid inducible (bai) operon encoding at least 9 open reading frames has been cloned and sequenced from this bacterium. The baiE gene from this operon has been subcloned and ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Dawson JA,Mallonee DH,Björkhem I,Hylemon PB

    更新日期:1996-06-01 00:00:00

  • Binding of hepatic lipase to heparin. Identification of specific heparin-binding residues in two distinct positive charge clusters.

    abstract::The interaction of hepatic lipase (HL) with heparan sulfate is critical to the function of this enzyme. The primary amino acid sequence of HL was compared to that of lipoprotein lipase (LPL), a related enzyme that possesses several putative heparin-binding domains. Of the three putative heparin-binding clusters of LPL...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Sendak RA,Berryman DE,Gellman G,Melford K,Bensadoun A

    更新日期:2000-02-01 00:00:00

  • Effects of high-glucose and high-fat diets on concanavalin A binding to rat liver plasma membranes and on the amount and pattern of their glycoprotein carbohydrates.

    abstract::Purified liver plasma membranes were prepared from rats fed a high-fat, carbohydrate-free diet or a high-glucose, fat-free diet. Membranes from rats fed the high-fat diet bound significantly less 125I-labeled concanavalin A (Con A) than did those from rats fed the fat-free diets. The magnitude of the binding differenc...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Henriquez DS,Tepperman HM,Tepperman J

    更新日期:1979-07-01 00:00:00

  • Archaebacterial ether lipid diversity analyzed by supercritical fluid chromatography: integration with a bacterial lipid protocol.

    abstract::A strategy has been developed for archaebacterial lipid analysis which provides three times the information to describe archaebacterial isolates and is compatible with simultaneous eubacterial/eukaryotic lipid analysis of environmental samples. Eubacterial and micro-eukaryotic biomass, community structure, and nutriti...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Hedrick DB,Guckert JB,White DC

    更新日期:1991-04-01 00:00:00

  • Differences in reactivity of antibodies to active versus inactive PLTP significantly impacts PLTP measurement.

    abstract::Due to conflicting reports concerning the relationship between phospholipid transfer protein (PLTP) activity and mass in plasma, the protein concentration and activity of PLTP were assessed in fractions isolated by fast protein liquid chromatography from the plasma of healthy normolipidemic individuals. Using both pol...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Murdoch SJ,Wolfbauer G,Kennedy H,Marcovina SM,Carr MC,Albers JJ

    更新日期:2002-02-01 00:00:00

  • TNF-α induces acyl-CoA synthetase 3 to promote lipid droplet formation in human endothelial cells.

    abstract::Chronic inflammation contributes to cardiovascular disease. Increased levels of the inflammatory cytokine, TNF-α, are often present in conditions associated with cardiovascular disease risk, and TNF-α induces a number of pro-atherogenic effects in macrovascular endothelial cells, including expression of adhesion molec...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.RA119000256

    authors: Jung HS,Shimizu-Albergine M,Shen X,Kramer F,Shao D,Vivekanandan-Giri A,Pennathur S,Tian R,Kanter JE,Bornfeldt KE

    更新日期:2020-01-01 00:00:00

  • Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia.

    abstract::Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion...

    journal_title:Journal of lipid research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1194/jlr.P800061-JLR200

    authors: Tremblay AJ,Lamarche B,Hogue JC,Couture P

    更新日期:2009-07-01 00:00:00

  • Selective uptake of HDL cholesteryl esters and cholesterol efflux from mouse peritoneal macrophages independent of SR-BI.

    abstract::Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M600136-JLR200

    authors: Brundert M,Heeren J,Bahar-Bayansar M,Ewert A,Moore KJ,Rinninger F

    更新日期:2006-11-01 00:00:00

  • A genome scan for serum triglyceride in obese nuclear families.

    abstract::Serum triglyceride (TG) levels are increased in extremely obese individuals, indicating abnormalities in lipid metabolism and insulin resistance. We carried out a genome scan for serum TG in 320 nuclear families segregating extreme obesity and normal weight. Three hundred eighty-two Marshfield microsatellite markers (...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M400391-JLR200

    authors: Li WD,Dong C,Li D,Garrigan C,Price RA

    更新日期:2005-03-01 00:00:00

  • Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.

    abstract::Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contain...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M003657

    authors: Subra C,Grand D,Laulagnier K,Stella A,Lambeau G,Paillasse M,De Medina P,Monsarrat B,Perret B,Silvente-Poirot S,Poirot M,Record M

    更新日期:2010-08-01 00:00:00

  • Effect of phospholipids and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones.

    abstract::Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. W...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Jüngst D,Lang T,Huber P,Lange V,Paumgartner G

    更新日期:1993-09-01 00:00:00

  • Lipid and apolipoprotein concentrations in prenodal leg lymph of fasted humans. Associations with plasma concentrations in normal subjects, lipoprotein lipase deficiency, and LCAT deficiency.

    abstract::The extent to which lipid and apolipoprotein (apo) concentrations in tissue fluids are determined by those in plasma in normal humans is not known, as all studies to date have been performed on small numbers of subjects, often with dyslipidemia or lymphedema. Therefore, we quantified lipids, apolipoproteins, high dens...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Nanjee MN,Cooke CJ,Olszewski WL,Miller NE

    更新日期:2000-08-01 00:00:00