Silencing of the mutant SCAP allele accounts for restoration of a normal phenotype in CT60 cells selected for NPC1 expression.

Abstract:

:The sterol regulatory element binding protein (SREBP)/SREBP cleavage-activating protein (SCAP) complex regulates the transcription of numerous genes involved in cellular cholesterol metabolism. The CHO mutant, CT60, and its parental cell line, 25RA, possess a gain-of-function mutation in one allele of the SCAP gene that renders the cells resistant to sterol-mediated suppression of cholesterol synthesis and uptake. In addition, CT60 cells do not express a functional Niemann-Pick type C1 (NPC1) protein, which leads to lysosomal accumulation of free cholesterol. Correction of the NPC1 defect by expression of a yeast artificial chromosome (YAC) containing the NPC1 genetic interval restored normal mobilization of cholesterol from the lysosomal compartment. Unexpectedly, the YAC-containing cell lines have overall cellular cholesterol concentrations that are comparable to wild-type levels, despite the assumed presence of the SCAP mutation. This phenotypic change results from a reduction in endogenous sterol synthesis, LDL receptor message, and HMG-CoA reductase message. Genetic analysis of the SCAP gene revealed that the YAC-expressing CT60 cells have normal regulation of these sentinel cholesterogenic genes as a result of selective silencing of the mutant SCAP allele, which appears to be independent of functional NPC1 expression.

journal_name

J Lipid Res

authors

Maguire JA,Reagan JW Jr

doi

10.1194/jlr.M500198-JLR200

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

1840-8

issue

9

eissn

0022-2275

issn

1539-7262

pii

M500198-JLR200

journal_volume

46

pub_type

杂志文章
  • The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter.

    abstract::The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary and intestinal removal of neutral sterols. Here, we identify a binding site for the orphan nuclear receptor liver receptor homolog-1 (LRH-1) at nt 134-142 of the ABCG5/ABCG8 intergenic region necessary for the activity of both the ABCG...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.C400002-JLR200

    authors: Freeman LA,Kennedy A,Wu J,Bark S,Remaley AT,Santamarina-Fojo S,Brewer HB Jr

    更新日期:2004-07-01 00:00:00

  • Quantitation of plasma lipids by gas-liquid chromatography on high temperature polarizable capillary columns.

    abstract::We have previously demonstrated the potential usefulness of capillary columns coated with a high temperature polarizable phenylmethylsilicone liquid phase in plasma lipid profiling (Kuksis, A., J.J. Myher, and P. Sandra. 1990. J. Chromatogr. 500: 427-441). The present study reports improved operating conditions along ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Kuksis A,Myher JJ,Geher K

    更新日期:1993-06-01 00:00:00

  • Functional characterization of a chimeric lipase genetically engineered from human lipoprotein lipase and human hepatic lipase.

    abstract::Lipoprotein lipase (LPL) and hepatic lipase (HL) mediate the hydrolysis of triglycerides and phospholipids present in circulating lipoprotein particles and are essential for normal lipid metabolism. Both enzymes have a similar primary amino acid structure and share requirements for intact catalytic, lipid binding, and...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Dichek HL,Parrott C,Ronan R,Brunzell JD,Brewer HB Jr,Santamarina-Fojo S

    更新日期:1993-08-01 00:00:00

  • Associations of human retinal very long-chain polyunsaturated fatty acids with dietary lipid biomarkers.

    abstract::The human retina is well-known to have unique lipid profiles enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and very long-chain polyunsaturated fatty acids (VLC-PUFAs) that appear to promote normal retinal structure and function, but the influence of diet on retinal lipid profiles in health and disease ...

    journal_title:Journal of lipid research

    pub_type: 临床试验,杂志文章

    doi:10.1194/jlr.P065540

    authors: Gorusupudi A,Liu A,Hageman GS,Bernstein PS

    更新日期:2016-03-01 00:00:00

  • Cholesterol crystal formation and growth in model bile solutions.

    abstract::Cholesterol monohydrate crystal formation was studied in supersaturated model bile solutions, containing unlabeled cholesterol, sodium cholate and soybean phosphatidylcholine, and tracer amounts of [3H]cholesterol. Solutions were either seeded with cholesterol crystals to initiate growth, or not seeded to allow self-n...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Whiting MJ,Watts JM

    更新日期:1983-07-01 00:00:00

  • Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.

    abstract::Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholest...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M053439

    authors: Zheng W,Mast N,Saadane A,Pikuleva IA

    更新日期:2015-01-01 00:00:00

  • COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes.

    abstract::Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-diHETE and 5,11-diHETE in isolated human leuk...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M017822

    authors: Tejera N,Boeglin WE,Suzuki T,Schneider C

    更新日期:2012-01-01 00:00:00

  • Human epidermal lipids: characterization and modulations during differentiation.

    abstract::Using thin-layer chromatography and glass capillary gas-liquid chromatography, we have quantitated the lipids in the germinative, differentiating, and fully cornified layers in human epidermis. As previously noted in nonhuman species, we found progressive depletion of phospholipids coupled with repletion of sterols an...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Lampe MA,Williams ML,Elias PM

    更新日期:1983-02-01 00:00:00

  • Zinc Finger Protein 202, genetic variation, and HDL cholesterol in the general population.

    abstract::Zinc Finger Protein 202 (ZNF202) is a transcriptional repressor that binds elements found predominantly in genes involved in HDL metabolism. We tested the following hypotheses: 1) frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in ZNF202 differ between individuals with low and high HDL cholesterol...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M500521-JLR200

    authors: Stene MC,Frikke-Schmidt R,Nordestgaard BG,Tybjaerg-Hansen A

    更新日期:2006-05-01 00:00:00

  • Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man.

    abstract::Studies on plasma triglycerides (TG) were performed in 10 nonobese and 16 obese patients with hypothyroidism and in 13 with hyperthyroidism. Nonobese, hypothyroid patients generally had normal levels of TG, but obese patients often had hypertriglyceridemia. In most hypothyroid patients 1-thyroxine treatment lowered pl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Abrams JJ,Grundy SM,Ginsberg H

    更新日期:1981-02-01 00:00:00

  • Lipoprotein lipase and acid lipase activity in rabbit brain microvessels.

    abstract::A preparation of cerebral microvessels was used to demonstrate the presence of lipoprotein lipase and acid lipase activity in the microvasculature of rabbit brain. Microvessels, consisting predominantly of capillaries, small arterioles, and venules, were islated from rabbit brain. Homogenates were assayed for lipolyti...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Brecher P,Kuan HT

    更新日期:1979-05-01 00:00:00

  • Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria.

    abstract::Maintaining cellular lipid homeostasis is crucial to oxidative tissues, and it becomes compromised in obesity. Lipid droplets (LD) play a central role in lipid homeostasis by mediating fatty acid (FA) storage in the form of triglyceride, thereby lowering intracellular levels of lipids that mediate cellular lipotoxicit...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M017939

    authors: Wang H,Sreenivasan U,Hu H,Saladino A,Polster BM,Lund LM,Gong DW,Stanley WC,Sztalryd C

    更新日期:2011-12-01 00:00:00

  • Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry.

    abstract::Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80 years while consuming diets generally low in cholesterol (mean intake = 226 +/- 126 mg/day). A new dual stable isotope method was used where a cholesterol tracer containing 6 extra mass units was given intravenously and another tracer with 5...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Bosner MS,Lange LG,Stenson WF,Ostlund RE Jr

    更新日期:1999-02-01 00:00:00

  • Differential scanning calorimetry and fluorescence probe investigations of very low density lipoprotein from the isolated perfused rat liver.

    abstract::Isolated rat livers were perfused at 37 degrees C with blood-free, defined medium containing delipidized bovine serum albumin (BSA), BSA-oleate, or BSA-palmitate. Very low density lipoproteins (VLDL) were isolated from the perfusate at 12 degrees C and lipid components were extracted and purified. Differential scannin...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Hale JE,Schroeder F

    更新日期:1981-07-01 00:00:00

  • Differential expression and function of ABCG1 and ABCG4 during development and aging.

    abstract::ABCG1 and ABCG4 are highly homologous members of the ATP binding cassette (ABC) transporter family that regulate cellular cholesterol homeostasis. In adult mice, ABCG1 is known to be expressed in numerous cell types and tissues, whereas ABCG4 expression is limited to the central nervous system (CNS). Here, we show sig...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/M900250-JLR200

    authors: Bojanic DD,Tarr PT,Gale GD,Smith DJ,Bok D,Chen B,Nusinowitz S,Lövgren-Sandblom A,Björkhem I,Edwards PA

    更新日期:2010-01-01 00:00:00

  • Prevention of low density lipoprotein aggregation by high density lipoprotein or apolipoprotein A-I.

    abstract::We have shown previously that low density lipoprotein (LDL) subjected to vortexing forms self-aggregates that are avidly phagocytosed by macrophages. That phagocytic uptake is mediated by the LDL receptor. We now show that LDL self-aggregation is strongly inhibited (80-95%) by the presence of high density lipoprotein ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Khoo JC,Miller E,McLoughlin P,Steinberg D

    更新日期:1990-04-01 00:00:00

  • Measurements of adipose tissue respiration in a closed chamber using an oxygen sensor: methodological considerations.

    abstract::A new polarographic system for measurement of oxygen consumption in vitro has been constructed to minimize different types of errors. The system was built of polyamide-6, Monax glass, stainless steel, and rubber to diminish oxygen leakage and gas capacitance properties. With these materials the system was gas-tight. N...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Hallgren P,Korsback S,Sjöström L

    更新日期:1986-09-01 00:00:00

  • Adiponectin forms a complex with atherogenic LDL and inhibits its downstream effects.

    abstract::Adiponectin, an adipocyte-derived protein, has antiatherogenic and antidiabetic effects, but how it confers the atherogenic effects is not well known. To study the antiatherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low density lipoprotein (LDL) to attenuate LDL's atherogenicit...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.RA120000767

    authors: Kakino A,Fujita Y,Ke LY,Chan HC,Tsai MH,Dai CY,Chen CH,Sawamura T

    更新日期:2020-11-21 00:00:00

  • Relationship between lipoprotein lipase and high density lipoprotein cholesterol in mice: modulation by cholesteryl ester transfer protein and dietary status.

    abstract::Plasma lipoprotein lipase (LPL) activity correlates with high density lipoprotein (HDL) cholesterol levels in humans. However, in several mouse models created either through transgenesis or targeted inactivation of LPL, no significant changes in HDL cholesterol values have been evident. One possible explanation for th...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Clee SM,Zhang H,Bissada N,Miao L,Ehrenborg E,Benlian P,Shen GX,Angel A,LeBoeuf RC,Hayden MR

    更新日期:1997-10-01 00:00:00

  • Measurement of lysophospholipid acyltransferase activities using substrate competition.

    abstract::Lysophospholipid acyltransferases (LPATs) incorporate fatty acyl chains into phospholipids via a CoA-dependent mechanism and are important in remodeling phospholipids to generate the molecular species of phospholipids found in cells. These enzymes use one lysophospholipid and one acyl-CoA ester as substrates. Traditio...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.D044636

    authors: Martin SA,Gijón MA,Voelker DR,Murphy RC

    更新日期:2014-04-01 00:00:00

  • Cyanidin-3-O-β-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model.

    abstract::Cyanidin-3-O-β-glucoside (C3G) (CAS number 7084-24-4), a typical anthocyanin pigment that exists in the human diet, has been reported to have anti-inflammatory properties. However, the effect of C3G on lipopolysaccharide (LPS)-induced mastitis and the molecular mechanisms have not been investigated. In this study, we ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M047340

    authors: Fu Y,Wei Z,Zhou E,Zhang N,Yang Z

    更新日期:2014-06-01 00:00:00

  • Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of glioma cell proliferation.

    abstract::Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatt...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.m200312-jlr200

    authors: Berge K,Tronstad KJ,Bohov P,Madsen L,Berge RK

    更新日期:2003-01-01 00:00:00

  • Apolipoprotein B(Arg3500----Gln) allele specific polymerase chain reaction: large-scale screening of pooled blood samples.

    abstract::A two-step polymerase chain reaction (PCR) method for the rapid detection of the apolipoprotein B(Arg3500----Gln) mutation in a mixture of pooled blood samples is described. In the first step PCR, a short gene fragment surrounding codon 3500 is amplified. Subsequently the reaction product is subjected to a second ampl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ruzicka V,März W,Russ A,Gross W

    更新日期:1992-10-01 00:00:00

  • Selective uptake of HDL cholesteryl esters is active in transgenic mice expressing human apolipoprotein A-I.

    abstract::The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Khoo JC,Pittman RC,Rubin EM

    更新日期:1995-03-01 00:00:00

  • Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants.

    abstract::Diet1 modulates intestinal production of the hormone, fibroblast growth factor (FGF)15, which signals in liver to regulate bile acid synthesis. C57BL/6ByJ mice with a spontaneous Diet1-null mutation are resistant to hypercholesterolemia compared with wild-type C57BL/6J mice through enhanced cholesterol conversion to b...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M078279

    authors: Lee JM,Ong JR,Vergnes L,de Aguiar Vallim TQ,Nolan J,Cantor RM,Walters JRF,Reue K

    更新日期:2018-03-01 00:00:00

  • Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration.

    abstract::The major net flux of cholesterol in the intact animal or human is from the peripheral organs to the liver. This flux is made up of cholesterol that is either synthesized in these peripheral tissues or taken up as lipoprotein cholesterol. This study investigates whether it is the concentration of apolipoprotein (apo) ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Jolley CD,Woollett LA,Turley SD,Dietschy JM

    更新日期:1998-11-01 00:00:00

  • Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells.

    abstract::Niemann-Pick C1-like 1 (NPC1L1) is a recently identified protein that mediates intestinal cholesterol absorption and regulates biliary cholesterol excretion. The itineraries and kinetics of NPC1L1 trafficking remain uncertain. In this study, we have visualized movement of NPC1L1-enhanced green fluorescent protein (NPC...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800145-JLR200

    authors: Petersen NH,Faergeman NJ,Yu L,Wüstner D

    更新日期:2008-09-01 00:00:00

  • Apolipoprotein A-I assayed in human serum by isotope dilution as a potential standard for immunoassay.

    abstract::We measured the amount of apoA-I in serum by isotope dilution, finding 1.33 mg/ml (standard deviation 0.177) in six normolipidemic, healthy subjects. We developed this method by adapting published techniques to purify apoA-I from 3 ml of serum in two steps: density gradient ultracentrifugation and high performance liq...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Weech PK,Jewer D,Marcel YL

    更新日期:1988-01-01 00:00:00

  • Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation.

    abstract::This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here,...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:10.1194/jlr.R700005-JLR200

    authors: Sethi JK,Vidal-Puig AJ

    更新日期:2007-06-01 00:00:00

  • Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia: a 31p NMR study.

    abstract::Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium ethylenediaminetetraaceti...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Moesgaard B,Jaroszewski JW,Hansen HS

    更新日期:1999-03-01 00:00:00