Abstract：
:Mutational inactivation of NPC1 largely blocks the movement of LDL-derived cholesterol from the lysosome to the metabolically active, cytosolic pool of sterol that is the substrate for steroid hormone production. Such a block might, in theory, lead to deficiencies in circulating levels of testosterone, progesterone, and corticosterone. However, there are at least two other sources for cellular cholesterol, de novo synthesis and scavenger receptor class B type I-mediated uptake of HDL cholesteryl ester (CE). In this study, we measured the rates of net cholesterol acquisition by these three pathways in the adrenal, ovary, and testis. In all three organs, the majority (81-98%) of cholesterol acquisition came from the selective uptake of CE from HDL and de novo synthesis. Furthermore, in the npc1(-/-)mouse, the cytosolic storage pool of CE in a tissue such as the adrenal remained constant (approximately 25 mg/g). As a result of these alternative pathways, the plasma concentrations of testosterone (3.5 vs. 2.5 ng/ml), progesterone (8.5 vs. 6.7 ng/ml), and corticosterone (391 vs. 134 ng/ml) were either the same or elevated in the npc1(-/-)mouse, compared with the control animal. Thus, impairment of cholesterol acquisition through the NPC1-dependent, clathrin-coated pit pathway did not limit the availability of cholesterol substrate for steroid hormone synthesis in the steroidogenic cells.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Xie C,Richardson JA,Turley SD,Dietschy JMdoi
10.1194/jlr.M500534-JLR200keywords:
subject
Has Abstractpub_date
2006-05-01 00:00:00pages
953-63issue
5eissn
0022-2275issn
1539-7262pii
M500534-JLR200journal_volume
47pub_type
杂志文章abstract：:The concentration dependence of the 500 MHz 1H-NMR spectra of taurocholate, taurochenodeoxycholate, taurodeoxycholate, and the monosulfate esters of taurochenodeoxycholate has been examined at 0.154 M NaCl in D2O. The resonances of the C18, C19, and C21 methyl groups and the C23 methylene group are differentially broa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE fr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M088153
更新日期：2018-11-01 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：:Lipoprotein lipase (LPL) hydrolyzes circulating lipoprotein triglyceride molecules while it is associated with the luminal surface of capillary endothelial cells. The precise molecular mechanism by which LPL attaches to these cells is unknown. LPL and a number of other molecules, including growth factors and clotting ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:A method is described for the determination of mevalonate in ultrafiltrates of blood plasma. The method depends on the phosphorylation of mevalonate with [gamma-32P]ATP and mevalonate kinase to 5-[32P]phosphomevalonate, and the subsequent isolation of the 5-[32P]phosphomevalonate together with known amounts of added 5...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:Pulmonary surfactant is a lipid:protein complex containing dipalmitoyl-phosphatidylcholine (DPPC) as the major component. Recent studies indicate adsorbed surfactant films consist of a surface monolayer and a monolayer-associated reservoir. It has been hypothesized that the monolayer and its functionally contiguous re...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200380-JLR200
更新日期：2003-03-01 00:00:00
abstract：:The major high density lipoprotein (HDL) apolipoprotein, apoA-I, was knocked out by gene targeting in ES cells to provide a model for the study of HDL metabolism and its relationship to plasma and tissue cholesterol metabolism. HDL and non-HDL cholesterol (HDL-C) were reduced in apoA-I-deficient mice. Feeding a high f...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Lysophospholipid (LP) research has experienced a period of renaissance with the discovery of the lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) receptors in the late 1990s. Vertebrate LP receptors regulate embryogenesis, vascular development, neurogenesis, uterine development, oocyte survival, immune ce...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800047-JLR200
更新日期：2009-04-01 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：:Serum triglyceride (TG) levels are increased in extremely obese individuals, indicating abnormalities in lipid metabolism and insulin resistance. We carried out a genome scan for serum TG in 320 nuclear families segregating extreme obesity and normal weight. Three hundred eighty-two Marshfield microsatellite markers (...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400391-JLR200
更新日期：2005-03-01 00:00:00
abstract：:Phospholipids serve as central structural components in cellular membranes and as potent mediators in numerous signaling pathways. There are six main classes of naturally occurring phospholipids distinguished by their distinct polar head groups that contain many unique molecular species with distinct fatty acid compos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D051581
更新日期：2014-11-01 00:00:00
abstract：:3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis, exists in one active (dephosphorylated) and one inactive (phosphorylated) form in liver microsomes obtained from several animal species. The present study was undertaken in order to dete...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:A molecular model was built for human lecithin:cholesterol acyltransferase (LCAT) based upon the structural homology between this enzyme and lipases (Peelman et al. 1998. Prot. Sci. 7: 585-597). We proposed that LCAT belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of a mix...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:The goal of this study was to determine whether apolipoprotein A-I (apoA-I) is lipidated before secretion by HepG2 cells. ApoA-I was extracted from microsomes after radiolabeling with [(35)S]Met/Cys. After ultracentrifugal flotation, d < 1.25 g/ml and d > 1.25 g/ml fractions were immunoprecipitated and analyzed by SDS...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2002-01-01 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：:Vitamin A-transporting protein in chicken plasma was purified by column chromatography on DEAE-Sephadex and Sephadex G-100; the protein formed a complex of retinol-binding protein (RBP) with prealbumin (PA). The molecular weight of the 1:1 molar complex was estimated to be 76,000 by gel filtration, and the sedimentati...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-05-01 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：:We have shown that expression of apolipoprotein (apo) C-III promotes VLDL secretion from transfected McA-RH7777 cells under lipid-rich conditions. To determine structural elements within apoC-III that confer to this function, we contrasted wild-type apoC-III with a mutant Ala23Thr originally identified in hypotriglyce...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M005108
更新日期：2010-06-01 00:00:00
abstract：:Liver cells isolated from normal and cholestyramine-treated rats were incubated as cell suspensions for up to 4 hr in a simple, defined medium. The bile acid concentration in cells plus cell medium was determined by gas-liquid chromatography. Normal hepatocytes synthesized cholic acid at an initial rate of 0.25 nmol/m...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-09-01 00:00:00
abstract：:The HDL Atherosclerosis Treatment Study (HATS) demonstrated a clinical benefit in coronary artery disease patients with low HDL cholesterol (HDL-C) levels treated with simvastatin and niacin (S-N) or S-N plus antioxidants (S-N+A) compared with antioxidants alone or placebo. Angiographically documented stenosis regress...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.M200439-JLR200
更新日期：2003-04-01 00:00:00
abstract：:Accumulation of foam cells in the neointima represents a key event in atherosclerosis. We previously demonstrated that Tanshinone IIA (Tan), a lipophilic bioactive compound extracted from Salvia miltiorrhiza Bunge, inhibits experimental atherogenesis, yet the detailed mechanisms are not fully understood. In this study...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M040394
更新日期：2014-02-01 00:00:00
abstract：:Cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200489-JLR200
更新日期：2003-05-01 00:00:00
abstract：:Rabbits were fed either 10% coconut oil, 10% coconut oil and 1% beta-sitosterol, 10% coconut oil and 1% cholesterol, or 10% coconut oil and 1% beta-sitosterol plus 1% cholesterol for 4 weeks. Microsomal membranes from intestines of animals fed the 1% beta-sitosterol diet had 48% less cholesterol and were enriched twof...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-04-01 00:00:00
abstract：:The 3-methyl-branched fatty acid phytanic acid is degraded by the peroxisomal alpha-oxidation route because the 3-methyl group blocks beta-oxidation. In adult Refsum disease (ARD), peroxisomal alpha-oxidation is defective, which is caused by mutations in the gene coding for phytanoyl-CoA hydroxylase in the majority of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400064-JLR200
更新日期：2004-07-01 00:00:00
abstract：:Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene identification 58, are causative for ichthyosis, a severe skin barrier disorder. Individuals with mutations in either of these genes show a defect in e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089771
更新日期：2018-12-01 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：:In late-stage atherosclerosis, much of the cholesterol in macrophage foam cells resides within enlarged lysosomes. Similarly, human macrophages incubated in vitro with modified LDLs contain significant amounts of lysosomal free cholesterol and cholesteryl ester (CE), which disrupts lysosomal function similar to macrop...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800659-JLR200
更新日期：2009-10-01 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：:Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P000331
更新日期：2010-02-01 00:00:00
abstract：:The CYP27A gene encodes a mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase, that is expressed in many different tissues and plays an important role in cholesterol and bile acid metabolism. In humans, CYP27A deficiency leads to cerebrotendinous xanthomatosis. To gain insight into the roles of CYP27A in the r...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400219-JLR200
更新日期：2005-01-01 00:00:00
