Abstract：
:Human apolipoprotein C-I (apoC-I) is an exchangeable apolipoprotein that binds to lipoprotein particles in vivo. In this study, we employed a LC-MS/MS assay to demonstrate that residues 38-51 of apoC-I are significantly protected from proteolysis in the presence of 1,2-dimyristoyl-3-sn-glycero-phosphocholine (DMPC). This suggests that the key lipid-binding determinants of apoC-I are located in the C-terminal region, which includes F42 and F46. To test this, we generated site-directed mutants substituting F42 and F46 for glycine or alanine. In contrast to wild-type apoC-I (WT), which binds DMPC vesicles with an apparent Kd [Kd(app)] of 0.89 microM, apoC-I(F42A) and apoC-I(F46A) possess 2-fold weaker affinities for DMPC with Kd(app) of 1.52 microM and 1.58 microM, respectively. However, apoC-I(F46G), apoC-I(F42A/F46A), apoC-I(F42G), and apoC-I(F42G/F46G) bind significantly weaker to DMPC with Kd(app) of 2.24 microM, 3.07 microM, 4.24 microM, and 10.1 microM, respectively. Sedimentation velocity studies subsequently show that the protein/DMPC complexes formed by these apoC-I mutants sediment at 6.5S, 6.7S, 6.5S, and 8.0S, respectively. This is compared with 5.0S for WT apoC-I, suggesting the shape of the particles was different. Transmission electron microscopy confirmed this assertion, demonstrating that WT forms discoidal complexes with a length-to-width ratio of 2.57, compared with 1.92, 2.01, 2.16, and 1.75 for apoC-I(F42G), apoC-I(F46G), apoC-I(F42A/F46A), and apoC-I(F42G/F46G), respectively. Our study demonstrates that the C-terminal amphipathic alpha-helix of human apoC-I contains the major lipid-binding determinants, including important aromatic residues F42 and F46, which we show play a critical role in stabilizing the structure of apoC-I, mediating phospholipid interactions, and promoting discoidal particle morphology.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
James PF,Dogovski C,Dobson RC,Bailey MF,Goldie KN,Karas JA,Scanlon DB,O'Hair RA,Perugini MAdoi
10.1194/jlr.M800529-JLR200subject
Has Abstractpub_date
2009-07-01 00:00:00pages
1384-94issue
7eissn
0022-2275issn
1539-7262pii
M800529-JLR200journal_volume
50pub_type
杂志文章abstract：:Phospholipase was isolated (in two fractions) from Vipera palestinae venom and it was shown to possess phospholipase A activity (hydrolyzing diacyl-sn-glycerophosphorylcholines, e.g., lecithin, in the 2-position) as well as lysophospholipase (phospholipase B) activity (hydrolyzing 1-monoacyl-sn-glycerophosphorylcholin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1973-05-01 00:00:00
abstract：:The ternary phase diagram of cholesteryl myristate--dimyristoyl lecithin--water has been determined by polarizing light microscopy, scanning calorimetry, and x-ray diffraction. Hydrated dimyristoyl lecithin forms a lamellar liquid--crystalline phase (L alpha) at temperatures greater than 23 degrees C into which limite...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:Choline glycerophospholipids and ethanolamine glycerophospholipids of ruminant skeletal muscle contain approximately 40% and 65% plasmalogen, respectively. In the 1,2-diacyl-sn-glycero-3-phosphocholine (diacyl CPG), 16:0-18:2(n-6) and 16:0-18:1(n-9) accounted for about 50% of the total molecular species; in the 2-acyl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The effect of various levels of the oral contraceptive drug, Enovid E, on serum and liver lipid levels of adult female rats has been investigated. Doses ranging from 0.052 to 1.04 mg/day have been employed in rats fed control or cholesterol-containing diets. It has been confirmed that after administration of even low,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-05-01 00:00:00
abstract：:Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-tra...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M067447
更新日期：2016-05-01 00:00:00
abstract：:Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M046961
更新日期：2014-12-01 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：:Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance ...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R008896
更新日期：2011-04-01 00:00:00
abstract：:Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation that acts primarily via a seven-transmembrane-spanning, G-protein-coupled receptor denoted BLT1. Here, we describe the synthesis and characterization of fluorescent analogs of LTB4 that are easy to produce, inexpensive, and without the disadvantages of a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500005-JLR200
更新日期：2005-06-01 00:00:00
abstract：:MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033779
更新日期：2013-09-01 00:00:00
abstract：:Two assays for the quantitative measurement of HMG-CoA reductase, the major regulatory enzyme in hepatic cholesterol biosynthesis, are described. The first of these procedures employs thin-layer chromatography (TLC) of the reaction product on plastic-backed silica gel G strips impregnated with ammonium carbonate. The ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:Cigarette smokers have reduced levels of plasma high density lipoprotein (HDL) compared to nonsmokers and are at risk of premature cardiovascular disease. Previous work from this laboratory has shown that exposure of human plasma to gas-phase cigarette smoke (CS) inhibited the activity of lecithin:cholesterol acyltran...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:We determined the effect of storage at -70 degrees C on the determination of plasma high density lipoprotein (HDL)-cholesterol. Plasma from 106 subjects was stored for 1, 6, and 12 months, then treated with heparin and MnCl2 to remove other lipoproteins, and HDL-cholesterol was measured. The mean HDL-cholesterol level...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Different batches of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) had varying amounts of contaminants which appeared to affect systematic biological studies. This contaminant was separated by silica gel column chromatography followed by high performance liquid chromatography and identified as 1,3-distearoyl-glyce...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054718
更新日期：2015-02-01 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：:Previous studies have indicated that a G to A substitution at position -76 in the gene encoding apolipoprotein A-I (apoA-I) confers increased plasma high density lipoprotein cholesterol (HDL-C). Increased HDL-C may be a direct consequence of the A allele, or may reflect the action of a locus in linkage disequilibrium ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:A variety of methods are currently used to analyze HL and LPL activities in mice. In search of a simple methodology, we analyzed mouse preheparin and postheparin plasma LPL and HL activities using specific polyclonal antibodies raised in rabbit against rat HL (anti-HL) and in goat against rat LPL (anti-LPL). As an alt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D700021-JLR200
更新日期：2007-12-01 00:00:00
abstract：:Synthesis of apolipoprotein (apo)E in hepatocytes leads to both secretion and retention in cell surface pools. Inclusion of Brefeldin A to HepG2 cells prompted a rapid decrease of cell surface apoE to about 37% of control values after a 3-h incubation. The t(1/2) for this dynamic pool was estimated to be 15 min. In co...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：:Apolipoproteins, such as apolipoprotein A-I (apoA-I), can stimulate cholesterol efflux from cells expressing the ATP binding cassette transporter A1 (ABCA1). The nature of the molecular interaction between these cholesterol acceptors and ABCA1 is controversial, and models suggesting a direct protein-protein interactio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300355-JLR200
更新日期：2004-02-01 00:00:00
abstract：:The role of lipid transfer proteins during plasma membrane biogenesis was explored. Developing amphibia embryos were used because during their growth an active plasma membrane biosynthesis occurs together with negligible mitochondrial and endoplasmic reticulum proliferation. Sonicated vesicles, containing 14C-labeled ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of F...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M038323
更新日期：2013-11-01 00:00:00
abstract：:Skeletal muscle has two circulatory routes, nutritive (in contact with muscle) and non-nutritive (part of which is located in the connective tissue), and the balance of flow between the two is controlled by neural input and circulating vasomodulators. The purpose of this study was to assess muscle triglyceride hydroly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:Previous studies have shown that colony stimulating factor-1 (CSF-1) deficiency dramatically reduced atherogenesis in mice. In this report we investigate this mechanism and explore a therapeutic avenue based on inhibition of CSF-1 signaling. Lesions from macrophage colony stimulating factor-1 (Csf1)+/- mice showed inc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M005215
更新日期：2010-07-01 00:00:00
abstract：:A lipid transfer particle (LTP) was isolated and purified from the hemolymph of the adult male American cockroach, Periplaneta americana, essentially according to the method previously developed for the purification of LTP from locust hemolymph. Fast protein liquid chromatography (FPLC) on a Mono Q column was used as ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Niemann-Pick type C (NPC) disease is a multisystem disorder resulting from mutations in the NPC1 gene that encodes a protein involved in intracellular cholesterol trafficking. Significant liver dysfunction is frequently seen in patients with this disease. The current studies used npc1 mutant mice to investigate the as...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600488-JLR200
更新日期：2007-04-01 00:00:00
abstract：:The behavior of human omental fat cells in vitro has been examined in order to define conditions under which glucose is converted to glyceride-glycerol and glyceride fatty acids. Synthesis of glyceride fatty acids from glucose reached maximal rates only after several hours of incubation in Krebs-Henseleit bicarbonate ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-05-01 00:00:00
abstract：:Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common -203A>C polymorphism in the CYP7A1 pro...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800364-JLR200
更新日期：2008-12-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) is a receptor-active lipid mediator with a broad range of biological effects. Ovarian cancer cells synthesize LPA, which promotes their motility, growth, and survival. We show that a murine homolog of a human protein previously reported to hydrolyze LPA is a highly selective detergent-stimu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300188-JLR200
更新日期：2003-10-01 00:00:00
abstract：:Oxidized low density lipoprotein (Ox-LDL) has a plethora of components that are not present in native LDL. Their presence and quantity depends on the nature, type, and extent of oxidation. Lipids esterified to oxidized fatty acids are the major components formed during the early phase of oxidation and these show a num...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：1999-12-01 00:00:00
