Abstract：
:Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). The strikingly more severe course of WD is caused by genetic defects of LAL that leave no residual enzymatic activity. Mutations at the exon 8/intron 8 transition of the LAL gene have been identified in several CESD and WD patients and are responsible for the manifestation of the disease. We have determined the genetic defect in a 3-month-old boy of African origin affected by WD. No enzymatic activity of the lysosomal acid lipase was detectable in white blood cells and cultured fibroblasts. Analysis of his LAL cDNA and genomic DNA revealed that he was homozygous for a mutation at position -3 of the exon 8 splice donor site. A C-->T transition leads to a nonsense codon and to a premature termination of the LAL protein at amino acid 277. Due to this mutation, a shorter LAL mRNA species was also generated that lacked exon 8 and was deficient of the nonsense codon. As a consequence, the protein synthesis proceeded to the natural termination codon, but the enzyme generated had an internal deletion of 24 amino acids (254-277) and was also inactive. These findings, together with our previous observations when analyzing the mutations in WD and CESD patients lead to the conclusion that the more severe WD is due to mutations that absolutely abolish lysosomal acid lipase (LAL) enzyme activity and the cholesteryl ester storage disease phenotype is due to mutations that allow some residual LAL activity to be manifested.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ries S,Aslanidis C,Fehringer P,Carel JC,Gendrel D,Schmitz Gsubject
Has Abstractpub_date
1996-08-01 00:00:00pages
1761-5issue
8eissn
0022-2275issn
1539-7262journal_volume
37pub_type
杂志文章abstract：:The apolipoprotein (apo) B-100-specific monoclonal antibody MB47 has been widely used in lipoprotein metabolism and atherosclerosis research. When bound to apoB-100 on low density lipoproteins (LDL), antibody MB47 completely blocks the binding of LDL to the LDL receptor. The epitope for antibody MB47 has previously be...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:We have studied the rate of phospholipid synthesis and turnover in mouse peritoneal macrophages in reaction to cholesterol influx and high density lipoprotein (HDL)-mediated cholesterol efflux, using three different radioactive precursors, 32PO4(3-), [3H]choline, and [14C]oleic acid. The cells were loaded with cholest...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:The role of plasma free fatty acids (FFA) in the transport of fatty acids from host tissues to Ehrlich ascites carcinoma in mice was studied. [9,10-(3)H] Palmitate complexed to mouse serum (albumin) was injected either intraperitoneally or intravenously into unanesthetized tumor-bearing mice. The incorporation of radi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-07-01 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：: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：: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：:We propose a simple mathematical model to account for the coupling of secretion rates of bile salts, lecithin, and cholesterol into bile. The model assumes that: 1) molecules of "biliary" lecithin and cholesterol enter a functional compartment located in the endoplasmic reticulum of the hepatocyte from which they are ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, sa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200405-JLR200
更新日期：2003-04-01 00:00:00
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
更新日期：2008-01-01 00:00:00
abstract：:Extracted tissue phospholipid 31P NMR profiles, obtained from individual porcine lenses subjected to two preservation procedures (acetone desiccation and freeze-drying) and a perchloric acid-extraction procedure, were compared to those from freshly excised lens specimens. Each profile yielded quantitative data on 12 l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-03-01 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
abstract：:Interactions of apolipoprotein A-I (apoA-I) with cell membranes appear to be important in the initial steps of reverse cholesterol transport. The objective of this work was to examine the effect of three distinct conformations of apoA-I (lipid-free and in 78 A or 96 A reconstituted high density lipoproteins, rHDL) on ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-02-01 00:00:00
abstract：:Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300091-JLR200
更新日期：2003-08-01 00:00:00
abstract：:Rod outer segments (ROSs) are specialized light-sensitive organelles in vertebrate photoreceptor cells. Lipids in ROS are of considerable importance, not only in providing an adequate environment for efficient phototransduction, but also in originating the second messengers involved in signal transduction. ROSs have t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R001891
更新日期：2010-04-01 00:00:00
abstract：:Supernatant protein factor (SPF) and anionic phospholipids such as phosphatidylglycerol (PG) stimulate squalene epoxidase activity in rat liver microsomes by promoting [3H]squalene uptake as well as substrate translocation (Chin, J., and K. Bloch. 1984. J. Biol. Chem. 259: 11735-11738). This process is postulated to b...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Serine palmitoyltransferase (SPT) catalyzes the rate-limiting step of condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (3KDS). Here, we report a HPLC-ESI-MS/MS method to directly quantify 3KDS generated by SPT. With this technique, we were able to detect 3KDS at a level comparable to that of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D078535
更新日期：2018-01-01 00:00:00
abstract：:Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafish npc1 and analyzed its gene ex...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M012377
更新日期：2011-07-01 00:00:00
abstract：:A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and dehydroepiandrosterone (DHEA-S) in rat brain. Using a solid-phase extraction recycling protocol, the results show that little or no PREG-S and DHEA-S (<1 pmol/g) is pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400244-JLR200
更新日期：2004-12-01 00:00:00
abstract：:HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmac...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073270
更新日期：2017-08-01 00:00:00
abstract：:The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is several times higher than expected from the sn-2 acyl composition of plasma phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much lower than expected. To explain these discrepancies, we proposed that LCAT transfe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400197-JLR200
更新日期：2004-12-01 00:00:00
abstract：:Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researc...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R500016-JLR200
更新日期：2006-02-01 00:00:00
abstract：:Serine palmitoyltransferase [EC 2.3.1.50] catalyzes the first unique reaction of sphingolipid biosynthesis. To determine whether or not different rat tissues are capable of initiating this pathway, its activity was determined for microsomes from rat liver, lung, brain, kidney, intestine, spleen, muscle, heart, pancrea...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:Four distinct subspecies of the insect hemolymph lipoprotein, lipophorin, that range in diacylglycerol (DAG) content from approximately 100 to 1000 molecules per particle, were treated with phospholipase C. Lipid analysis demonstrated that both phosphatidylcholine and phosphatidylethanolamine were hydrolyzed to DAG. P...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Serum amyloid P (SAP) is a common component of human amyloid deposits and has been identified in atherosclerotic lesions. We investigated the extent of the colocalization of SAP with apolipoprotein A-I (apoA-I), apoB, apoC-II, and apoE in human coronary arteries and explored potential roles for SAP in these regions, s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700098-JLR200
更新日期：2007-10-01 00:00:00
abstract：:A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c 9,t11) and trans10, cis12 (t10,c12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300120-JLR200
更新日期：2003-08-01 00:00:00
abstract：:The kinetics of lecithin exchange between native lipoproteins was characterized for individual molecular species of lecithins of rat mesenteric lymph chylomicrons and rat plasma HDL. Studies were performed in the absence of lipid transfer proteins. Donor (chylomicrons) and acceptor (HDL) particles were present in rati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:Cerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis in which symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed a new dried blood ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P075051
更新日期：2017-05-01 00:00:00
abstract：:The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082362
更新日期：2018-02-01 00:00:00
abstract：:Biliary secretion of bile acid glucuronides was studied in control rats and in rats with a congenital defect in hepatobiliary transport of organic anions (GY rats). In control animals, hepatobiliary transport of [3H]lithocholic acid 3-O-glucuronide and [3H]cholic acid 3-O-glucuronide was efficient (greater than 95% in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-12-01 00:00:00
