Abstract:
:The identification of three highly conserved phosphorylation sites in the cytoplasmic domain of each of the monomeric subunits of the macrophage scavenger receptor suggests that protein phosphorylation may regulate this receptor pathway. To investigate this, mouse peritoneal macrophages were pretreated with either the protein phosphatase inhibitor okadaic acid or the protein kinase inhibitor staurosporine to modulate cellular protein phosphorylation and their effects on the metabolism of acetyl-LDL were measured. Both okadaic acid and staurosporine inhibited the degradation of acetyl-low density lipoprotein (LDL) without affecting cellular lactic dehydrogenase (LDH) levels. The inhibition by okadaic acid was due to a 70% decrease in acetyl-LDL binding whereas post-receptor processing was minimally affected. Calyculin A, another serine/threonine phosphatase inhibitor, also reduced acetyl-LDL binding, whereas lithium chloride, an inositol phosphatase inhibitor, did not. Okadaic acid did not decrease steady state receptor mRNA levels nor decrease the number of total cellular receptors, consistent with a posttranslational mechanism of action. Interestingly, protease sensitivity studies showed that the receptors were still located on the cell surface. These studies suggest that okadaic acid inhibits acetyl-LDL binding by causing the redistribution of surface receptors into a sequestered compartment or inactivating the receptors. In contrast, staurosporine produced a paradoxical increase in receptor expression (30%) but slowed post-receptor processing (2.3-fold decrease). The latter was due to an inhibition of ligand internalization (2.9-fold decrease) via a protein kinase C-independent mechanism. Macrophage pinocytosis was also slowed by staurosporine (38% decrease); however, this does not appear to account for the inhibition of scavenger receptor internalization. Direct receptor phosphorylation was also slowed by staurosporine (38% decrease); however, this does not appear to account for the inhibition of scavenger receptor internalization. Direct receptor phosphorylation was also investigated and it was established that the receptor can be phosphorylated; however, changes in receptor function did not correlate with changes in the degree of receptor phosphorylation. Together these studies demonstrate that changes in cellular protein phosphorylation affect the expression, surface transport, and internalization of the macrophage scavenger receptor and suggest that the regulated phosphorylation/dephosphorylation of cellular proteins may be an important biochemical mechanism that controls normal processing of ligands by this receptor pathway.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Fong LGsubject
Has Abstractpub_date
1996-03-01 00:00:00pages
574-87issue
3eissn
0022-2275issn
1539-7262journal_volume
37pub_type
杂志文章abstract::Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understoo...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M083899
更新日期:2018-08-01 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::Cerebrosides have been isolated from adult human aortic tissue. Each aorta was divided into portions classified as normal, fatty streaks, fibrous plaques, or complicated lesions. The cerebrosides were isolated by Florisil column chromatography, mild alkaline methanolysis, a second Florisil column, and preparative thin...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1968-07-01 00:00:00
abstract::The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of 3H2O and [14C]mevalonate into digitonin-precipitable sterols with time of...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::A method for apolipoprotein (apo) E genotyping was developed using the polymerase chain reaction (PCR) with allele-specific oligonucleotide primers (ASP). Synthetic oligonucleotides with base-pair mismatches at the 3' terminus were used as primers to amplify the apoE gene in subjects previously phenotyped using isoele...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were det...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 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::Compared with classic essential fatty acid deficiency or the feeding of a fat-free diet, little is known about specific linoleate deficiency in the rat. Carbon recycling into de novo lipogenesis has been reported to be an obligatory feature of linoleate metabolism in the liver, even in extreme linoleate deficiency (LA...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The surface area, A, of contracting fatty acid monolayers was measured as a function of time, t, at constant surface pressure. In the initial temporal phase, ln A was linear with radical t. In a subsequent steady-state phase, ln A was linear with t. The initial desorption coefficient for sodium palmitate, K(i), and th...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1973-01-01 00:00:00
abstract::In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate specie...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M019927
更新日期:2012-01-01 00:00:00
abstract::The objective of this study was to investigate the mobilization of individual fatty acids from human subcutaneous adipose tissue in vivo. Concentrations of individual non-esterified fatty acids were measured in arterialized plasma and in the venous drainage from subcutaneous abdominal adipose tissue in eight normal su...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The metabolism of chenodeoxycholic acid by Pseudomonas sp. NCIB 10590 under strict anaerobic conditions was studied. A range of unsaturated acidic and neutral metabolites were isolated and identified. The major acidic product was chola-4,6-dien-3-one-24-oic acid whilst the major neutral product was androsta-4,6-dien-3...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated. In addition to its historically wel...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.S092007
更新日期:2019-04-01 00:00:00
abstract::Sulfoquinovosyl diglyceride from plant tissues is recovered in sizeable quantities, free from phospholipids and galactolipids. ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1966-07-01 00:00:00
abstract::Taurocholate, a relatively hydrophobic bile salt, is a potent down-regulator of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase (C7 alpha H), the rate-determining enzymes of the cholesterol and bile acid biosynthetic pathways, respectively. Inhibition of cholesterol synthesis with a bolus dose of mevinolin (lova...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1992-05-01 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::The role of phosphodiesterase in glucagon resistance of large adipocytes was investigated. A comparison was made of phosphodiesterase activities of homogenates prepared from isolated small (mean diameter approximately 45 micro m) and large (mean diameter approximately 78 micro m) adipocytes, using various concentratio...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1974-01-01 00:00:00
abstract::Previous studies have demonstrated that perturbations in barrier function stimulate epidermal lipid synthesis and that this increase can be prevented by occlusive membranes. These observations suggest that epidermal lipid synthesis might be related to barrier function and raised the question whether transcutaneous wat...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1989-03-01 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::Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::To assess the possible role of altered hepatic processing of free fatty acids in dietary sucrose-induced accumulation of triglyceride in the liver and blood plasma, livers from rats fed commercial laboratory stock and high sucrose diets were perfused both with and without oleic acid substrate. Consumption of the sucro...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::The increased generation of reactive oxygen species that occurs in the condition of obesity may be responsible for oxidative injury to erythrocyte membranes, which could lead to a decrease in tissue oxygenation. Therefore, we have looked into the effects of obesity on both indexes of oxidative damage and physical-chem...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300509-JLR200
更新日期:2004-10-01 00:00:00
abstract::Activation of cultured hepatic stellate cells correlated with an enhanced expression of proteins involved in uptake and storage of fatty acids (FA translocase CD36, Acyl-CoA synthetase 2) and retinol (cellular retinol binding protein type I, CRBP-I; lecithin:retinol acyltransferases, LRAT). The increased expression of...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M200376-JLR200
更新日期:2003-02-01 00:00:00
abstract::Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly exp...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M800666-JLR200
更新日期:2009-06-01 00:00:00
abstract::Triglyceride-rich lipoproteins derived from ten normo- and hyperlipidemic apoE-2 homozygotes were analyzed for their composition, beta-VLDL content, and their ability to induce cholesteryl ester storage in macrophages. In six of these probands apoE sequence analysis revealed that the cysteine residues were at position...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Loss of function of Niemann-Pick C1 (NPC1) leads to lysosomal free cholesterol storage, resulting in the neurodegenerative disease Niemann-Pick disease type C (NPC). Significant numbers of patients with NPC also suffer from liver disease. Currently, no treatments exist that alter patient outcome, and it is unknown if ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M007211
更新日期:2010-08-01 00:00:00
abstract::The proton NMR spectra of the N-methyl choline region of normal and lecithin:cholesterol acyltransferase (LCAT)-deficient lipoproteins and of egg yolk phosphatidylcholine-cholesterol 55:45 (mol %) vesicle mixtures have been examined in the presence and absence of manganous sulfate as a line-broadening reagent. Mangano...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::The formation of cholic acid from 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA) was studied in two normal subjects. [3H]THCA and [14C]cholic acid were administered intravenously by simultaneous injection and the specific activities (percent injected amount/mumol) of [3H]- and [14C]cholic acid w...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized placebo-controlled double-blind crossover tri...
journal_title:Journal of lipid research
pub_type: 杂志文章,随机对照试验
doi:10.1194/jlr.M076901
更新日期:2017-11-01 00:00:00
abstract::We have defined the lipid composition of copper-oxidized LDL (Cu-oxLDL) and a macrophage-foam cell model generated by the uptake of this modified lipoprotein. An HPLC method previously developed by our group for the measurement of lipid oxidation products of LDL was extended to permit the analysis of an array of 7-ket...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00