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 Resjournal_title
Journal of lipid researchauthors
Maguire JA,Reagan JW Jrdoi
10.1194/jlr.M500198-JLR200keywords:
subject
Has Abstractpub_date
2005-09-01 00:00:00pages
1840-8issue
9eissn
0022-2275issn
1539-7262pii
M500198-JLR200journal_volume
46pub_type
杂志文章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
更新日期:2004-07-01 00:00:00
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:
更新日期:1993-06-01 00:00:00
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:
更新日期:1993-08-01 00:00:00
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
更新日期:2016-03-01 00:00:00
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:
更新日期:1983-07-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2012-01-01 00:00:00
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:
更新日期:1983-02-01 00:00:00
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
更新日期:2006-05-01 00:00:00
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:
更新日期:1981-02-01 00:00:00
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:
更新日期:1979-05-01 00:00:00
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
更新日期:2011-12-01 00:00:00
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:
更新日期:1999-02-01 00:00:00
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:
更新日期:1981-07-01 00:00:00
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
更新日期:2010-01-01 00:00:00
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:
更新日期:1990-04-01 00:00:00
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:
更新日期:1986-09-01 00:00:00
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
更新日期:2020-11-21 00:00:00
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:
更新日期:1997-10-01 00:00:00
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
更新日期:2014-04-01 00:00:00
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
更新日期:2014-06-01 00:00:00
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
更新日期:2003-01-01 00:00:00
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:
更新日期:1992-10-01 00:00:00
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:
更新日期:1995-03-01 00:00:00
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
更新日期:2018-03-01 00:00:00
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:
更新日期:1998-11-01 00:00:00
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
更新日期:2008-09-01 00:00:00
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:
更新日期:1988-01-01 00:00:00
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
更新日期:2007-06-01 00:00:00
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:
更新日期:1999-03-01 00:00:00