Abstract：
:Deficiency of lysosomal acid lipase (LAL) leads to either Wolman disease (WD) or the more benign cholesteryl ester storage disease (CESD). To identify the molecular basis of the different phenotypes we have characterised the LAL gene mutations in three new patients with LAL deficiency. A patient with WD was homozygote for a null allele Y303X. The other two patients, with CESD, presented either homozygosity for T267I or compound heterozygosity consisting of Q64R and an exon 8 donor splice site substitution (G-->A in position -1). The mutants T267I and Q64R and the previously reported L273S, G66V, and H274Y CESD substitutions, overexpressed in stable clones, were found to be fully glycosylated and show an enzymatic activity of 3-8% of that of normal LAL. On the other hand, the delta254-277 mutant protein derived from exon 8 skipping and the Y303X protein were totally inactive. By transient transfection of hybrid minigene constructs, the CESD G-->A (-1) substitution resulted in partial exon inclusion, thus allowing the production of a small amount of normal LAL mRNA and hence of a functional enzyme. In contrast, a G-->A substitution observed in WD at position + 1 of the same exon 8 donor site resulted in complete exon skipping and the sole production of an inactive delta254-277 protein. In conclusion, LAL genotypes determine the level of residual enzymatic activity, thus explaining the severity of the phenotype.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Pagani F,Pariyarath R,Garcia R,Stuani C,Burlina AB,Ruotolo G,Rabusin M,Baralle FEsubject
Has Abstractpub_date
1998-07-01 00:00:00pages
1382-8issue
7eissn
0022-2275issn
1539-7262journal_volume
39pub_type
杂志文章abstract：:Baboons possess Lp[a] that is similar to human Lp[a], including the presence of the unique protein, apo[a]. Baboon apo[a] occurred in at least nine isoforms distinguishable by size. Isoforms were resolved by 3-12% polyacrylamide gradient gel electrophoretic separation of serum proteins, and were detected with baboon a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200386-jlr200
更新日期：2002-12-01 00:00:00
abstract：:In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca(2+)-independent phospholipase A(2) (iPLA(2)), Ca(2+)-independent plasmalogen PLA(2) or secretory PLA(2 (sPLA2)), but not by Ca(2+)-dependent cytosolic PLA(2) (cPLA2), which selectively releases arachidonic acid (AA)....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M006262
更新日期：2010-08-01 00:00:00
abstract：:Lipoproteins internalized by the LDL receptor (LDLR) are released from this receptor in endosomes through a process that involves acid-dependent conformational changes in the receptor ectodomain. How acidic pH promotes this release process is not well understood. Here, we assessed roles for six histidine residues for ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M070938
更新日期：2017-02-01 00:00:00
abstract：:Described herein are the chemical syntheses of a number of deuterated derivatives of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one. These include the [2,2,3 alpha,4,4,7,7,9 alpha,16,16-2H10]-, [7 alpha,9 alpha,16,16-2H4]-, [7,7,9 alpha,16,16-2H5]-, and [2,2,3 alpha,4,4-2H5]-analogs of the delta 8(14)-15-ketosterol. Also i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. To study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (LDL) to attenuate LDL's ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-03 00:00:00
abstract：:The reversibility and regression of histological and biochemical findings in a mouse model of Gaucher disease (4L/PS-NA) was evaluated using a liver-enriched activator protein promoter control of a tetracycline-controlled transcriptional activation-responsive human acid beta-glucosidase (hGCase) transgenic system. 4L/...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600239-JLR200
更新日期：2006-10-01 00:00:00
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
更新日期：2018-06-01 00:00:00
abstract：:To study the mechanism of alcoholic hypertriglyceridemia, baboons were pair-fed liquid diets containing 50% of energy as ethanol or as additional carbohydrate for 5-16 months. Alcohol-fed animals developed hypertriglyceridemia and early stages of alcoholic injury, namely fatty liver with or without perivenular fibrosi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:Pancreatic triglyceride lipase (PTL) and its protein cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. PLR...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.r200012-jlr200
更新日期：2002-12-01 00:00:00
abstract：:The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previousl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034124
更新日期：2013-04-01 00:00:00
abstract：:Familial hypobetalipoproteinemia (FHBL) exists in three forms: a) FHBL genetically linked to truncated forms of apolipoprotein B (apoB); b) FHBL linked to the apoB gene but with no apoB truncations; and c) FHBL not linked to the apoB gene. Mean production rate (PR) of apoB-100 in FHBL subjects heterozygous for apoB tr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:Various properties of retinyl ester hydrolysis in the liver and the retinal pigment epithelium (RPE) have been studied, yet the relationship between the retinyl ester hydrolase (REH) activities in these tissues of the same species is not known. In the present study, REH activities in bovine liver and RPE microsomes we...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Binding of the medium-chain fatty acids (MCFA), octanoic (OCT) and decanoic (DEC) acid, to human serum albumin (HSA) has been studied by 13C NMR spectroscopy. NMR spectra at 35 degrees C showed an apparently homogeneous binding environment (a single, narrow resonance for the 13C-enriched carboxyl carbon) at different ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:The phospholipase A2(PLA2) activity of peroxiredoxin (Prdx)6 has important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064758
更新日期：2016-04-01 00:00:00
abstract：:Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-throug...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000312
更新日期：2020-06-01 00:00:00
abstract：:We have studied the synthesis, modification, and secretion of rat apoE in primary cultures of neonatal aortic smooth muscle cells and adult rat hepatocytes. The cultures were pulsed with [35S]methionine and the intracellular and secreted apoE were immunoprecipitated and analyzed by two-dimensional isoelectric focusing...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control d...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2001-12-01 00:00:00
abstract：:We have reported the use of a retroviral vector to introduce the low density lipoprotein (LDL) receptor gene into receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbit fibroblasts (Miyanohara, A., M. F. Sharkey, D. Steinberg, J. L. Witztum, and T. Friedmann. 1988. Proc. Natl. Acad. Sci. USA. 85: 6538-6542...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Most mammalian neoplasms have a defect in ether lipid content manifested by the presence of abnormally large quantities of 0-alkyl glyceryl ethers, in contrast to normal tissues in which the alk-1-enyl structure predominates. These lipids are for the most part structural. The manner in which tumor cell plasma membrane...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:We describe a method for estimating the total activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34) in the small intestine of rats. An homogenate of the whole small intestine is prepared rapidly and assayed directly to maximize the yield of enzyme and to minimize opportunity for uncontrolled cha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-02-01 00:00:00
abstract：:Male Sprague-Dawley rats were fed diets that contained 20% by weight soybean oil or rapeseed oil (21% and 43% erucic acid) for 7 days. The rapeseed oil diets increased the cardiac triacylglycerol content 5-fold and 25-fold, respectively, above control values. Hearts were removed from the animals and perfused with modi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:SW-13 adrenal tumor cells that lack detectable intermediate filaments (IF-free) exhibit an impaired capacity to esterify lipoprotein-derived cholesterol compared with cells that contain vimentin filaments. IF-free cells were found to synthesize and secrete significant amounts of apoE, while apoE secretion was nearly u...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has been observed in various pathological conditions, including atherosclerosis. However, the biological roles of PCOOH in these conditions remain unknown. To estimate the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800582-JLR200
更新日期：2009-05-01 00:00:00
abstract：:Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
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). T...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800529-JLR200
更新日期：2009-07-01 00:00:00
abstract：:To study the mechanisms of hepatic HDL formation, we investigated the roles of ABCA1, ABCG1, and SR-BI in nascent HDL formation in primary hepatocytes isolated from mice deficient in ABCA1, ABCG1, or SR-BI and from wild-type (WT) mice. Under basal conditions, in WT hepatocytes, cholesterol efflux to exogenous apoA-I w...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M017079
更新日期：2012-03-01 00:00:00
abstract：:We report on the effect of human apolipoprotein (apo) A-II transgene expression on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose plasma human apoA-II concentrations (approximately 23 and 96 mg/dl, respectively) span the normal range in humans. After 9 months of an atherogenic diet, 25.3 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
