Abstract:
:When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Mabs) against functional domains of apoA-I. Size exclusion chromatography of HDL(3) revealed that proteolysis for up to 24 h did not alter the integrity of the alpha-migrating HDL, whereas a minor peak containing particles of smaller size with prebeta mobility disappeared after as little as 15 min of incubation. At the same time, generation of a large (26 kDa) polypeptide containing the N-terminus of apoA-I was detected. This large fragment and other medium-sized fragments of apoA-I produced after prolonged treatment with chymase were found to be associated with the alphaHDL; meanwhile, small lipid-free peptides were rapidly produced. Incubation of HDL(3) with chymase inhibited binding of Mab A-I-9 (specific for prebeta(1)HDL) most rapidly (within 15 min) of the eight studied Mabs. This rapid loss of binding was paralleled by a similar reduction in the ability of HDL(3) to induce high-affinity efflux of cholesterol from macrophage foam cells, indicating that proteolysis had destroyed an epitope that is critical for this function. In sharp contrast, prolonged degradation of HDL(3) by chymase failed to reduce the ability of HDL(3) to activate LCAT, even though it led to modification of three epitopes in the central region of apoA-I that are involved in lecithin cholesterol acyltransferase (LCAT) activation. This differential sensitivity of the two key functions of HDL(3) to the proteolytic action of mast cell chymase is compatible with the notion that, in reverse cholesterol transport, intactness of apoA-I is essential for prebeta(1)HDL to promote the high-affinity efflux of cellular cholesterol, but not for the alpha-migrating HDL particles to activate LCAT.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Lee M,Uboldi P,Giudice D,Catapano AL,Kovanen PTkeywords:
subject
Has Abstractpub_date
2000-06-01 00:00:00pages
975-84issue
6eissn
0022-2275issn
1539-7262journal_volume
41pub_type
杂志文章abstract::The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::Native interactions between lysophospholipids (LPs) and their cognate LP receptors are difficult to measure because of lipophilicity and/or the adhesive properties of lipids, which contribute to high levels of nonspecific binding in cell membrane preparations. Here, we report development of a free-solution assay (FSA)...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D120000880
更新日期:2020-08-01 00:00:00
abstract::Human apolipoprotein (apo) E occurs as three common isoforms (apoE4, E3, and E2), all of which influence plasma cholesterol levels. Although both apoE4 and E3 bind with equal effectiveness to the low density lipoprotein receptor, they associate preferentially with different classes of plasma lipoproteins: apoE4 with v...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::The fatty acid transport protein (FATP) Fat1p in the yeast Saccharomyces cerevisiae functions in concert with acyl-coenzyme A synthetase (ACSL; either Faa1p or Faa4p) in vectorial acylation, which couples the transport of exogenous fatty acids with activation to CoA thioesters. To further define the role of Fat1p in t...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M700300-JLR200
更新日期:2007-11-01 00:00:00
abstract::A subgroup of peroxisomal disorders, peroxisome biogenesis defects (PBD), can be differentiated by elevated levels of C(27) bile acids in plasma and bile. Patients with peroxisomal disorders, who lack the ability to chain-shorten the C(27) bile acid intermediates into C(24) bile acids, show elevated levels of C(27) bi...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 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 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::Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-bin...
journal_title:Journal of lipid research
pub_type: 临床试验,杂志文章
doi:10.1194/jlr.P009860
更新日期:2010-11-01 00:00:00
abstract::The absorption and distribution of deuterated trans- and cis-13-octadecenoic acid (13t-18:1 and 13c-18:1) in plasma lipids were compared to deuterated cis-9-octadecenoic acid (9c-18:1) in two young adult male subjects. A mixture of triglycerides was fed in a multiple-labeled experiment where each triglyceride containe...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::We studied the effects of the lecithin:cholesterol acyltransferase reaction on the size and composition of the small spherical high density lipoproteins of patients afflicted with familial lecithin:cholesterol acyltransferase deficiency. We isolated these lipoproteins by preparative ultracentrifugation and rate zonal ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::Lilly PCSK9 antibody LY3015014 (LY) is a monoclonal antibody (mAb) that neutralizes proprotein convertase subtilisin-kexin type 9 (PCSK9). LY decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum. Comparing the epitope of LY with other clinically tes...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M061903
更新日期:2015-11-01 00:00:00
abstract::The fatty acid composition of human skin fibroblasts grown in 10% dialyzed fetal calf serum can be modified considerably by adding supplemental fatty acids to the culture medium. The degree of modification was dependent on the concentration of added fatty acid over the range tested, 2.5 X 10(-5) to 1 X 10(-4) M. At th...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1979-05-01 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::Conditions leading to oxidation of LDL in vivo are still unknown. While the occurrence of oxidized lipoproteins and catalytic free iron in advanced atherosclerotic lesions has been demonstrated, the origin of both is unclear. In vivo, iron metabolism is tightly regulated by iron-binding proteins that ensure that virtu...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::We analysed the sensitivity to beta-adrenoceptor agonists in epididymal adipose cells from rats submitted to a stress protocol previously reported to induce alterations in sensitivity to catecholamines in cardiac tissue from rats. Food intake and body weight were lower, whereas adipocytes basal lipolysis was higher (c...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::In mammals, because they share a single synthetic pathway, n-6/n-3 ratios of dietary PUFAs impact tissue arachidonic acid (ARA) and DHA content. Likewise, SNPs in the human fatty acid desaturase (FADS) gene cluster impact tissue ARA and DHA. Here we tested the feasibility of using heterozygous Fads2-null-mice (HET) as...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M064956
更新日期:2016-11-01 00:00:00
abstract::Polyunsaturated fatty acids, including docosahexaenoic acid (DHA, 22:6n-3), modulate immune responses and exert beneficial immunosuppressive effects, but the molecular mechanisms inhibiting T-cell activation are not yet elucidated. Lipid rafts have been shown to play an important role in the compartmentalization and m...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500033-JLR200
更新日期:2005-09-01 00:00:00
abstract::High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tiss...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P000935
更新日期:2010-05-01 00:00:00
abstract::Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::LDL receptor-null (LDLR(-/-)) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR(-/-)mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M700433-JLR200
更新日期:2008-01-01 00:00:00
abstract::The sialic acid present in erythrocyte ghosts was estimated by methane chemical ionization mass fragmentography of the trimethylsilyl methyl glycosides. The internal standard was 3,4,6-tris-trimethylsilyl-alpha-phenyl-2-deoxy-2-acetamide-D-glucosaminide, as proposed by Yu and Ledeen (J. Lipid Res. 1970. 11: 506-516). ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::A rapid and accurate method is described for the assay of cholesterol ester hydrolase (CEH) activity. Aliquots of the enzyme-substrate incubation mixture are extracted into isopropanol. The free cholesterol concentration in each extract is determined enzymatically using a single aqueous reagent containing cholesterol ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1978-09-01 00:00:00
abstract::NADPH-dependent lipid peroxidation in liver microsomes, as measured by malondialdehyde formation, decreased by 90% when rats were fed a diet containing 16% coconut oil. This reduction occurred within 1 to 3 days after the rats were placed on this highly saturated diet. The decrease in peroxidation activity was associa...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract::The facile synthesis of lithocholic acids sulfates by a procedure that produced the desired products in over 90% yield is described. Lithocholic acid sulfate and glycolithocholic acid sulfate were synthesized by reacting lithocholic acid or glycolithocholic acid with sulfur trioxide-triethylamine complex in dimethylfo...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract::Cellular cholesterol is known to be under homeostatic control in nonsteroidogenic cells, and this intrigued us to understand how such control works in steroidogenic cells that additionally use cholesterol for steroid hormone synthesis. We employed primary culture of rat ovarian granulosa cells to study how steroidogen...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M030239
更新日期:2013-02-01 00:00:00
abstract::Reduced estrogen levels result in loss of protection from coronary heart disease in postmenopausal women. Enhanced and diminished atherosclerosis have been associated with plasma levels of cholesteryl ester transfer protein (CETP); however, little is known about the role of CETP-ovarian hormone interactions in atherog...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m100440-jlr200
更新日期:2003-01-01 00:00:00
abstract::We previously have shown that LDL-R354, a truncated low density lipoprotein (LDL) receptor, is a calcium binding protein. LDL-R354 is composed of the ligand binding domain and repeat A of the EGF precursor homology domain of the full-length human LDL receptor. We also found that Ca2+ was required for the interaction b...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::The rate of peroxidation of unconjugated bilirubin (UCB), catalyzed by horseradish peroxidase (HRP), has been employed by Jacobsen (1969. FEBS Lett. 5: 112-114) to assess the fraction of unbound UCB in the presence of serum albumin. We used this method to examine the interactions of UCB with taurocholate (TC) at pH 8....
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Lipid concentrations are heritable traits. Recently, the number of known genetic loci associated with lipid levels in adults increased from 95 to 157. The effects of these 157 loci have not been tested in children. Considering that lipid levels track from childhood to adulthood, we studied to determine whether these v...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P066902
更新日期:2016-12-01 00:00:00
abstract::To assess the relationship between cholesterol synthesis and feedback inhibition of bile acid synthesis, we studied seven normal human subjects taking three different doses of chenodiol, 0, 5, and 15 mg/kg per day: once while taking no lovastatin and again while taking lovastatin 80 mg/day. Lovastatin and both doses o...
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:1994-08-01 00:00:00