Abstract：
:In specialized cell types, lysosome-related organelles support regulated secretory pathways, whereas in nonspecialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol-storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Here, we report that cyclodextrin triggers the secretion of the endo/lysosomal content in nonspecialized cells and that this mechanism is responsible for the decreased cholesterol overload in Niemann-Pick type C cells. We also find that the secretion of the endo/lysosome content occurs via a mechanism dependent on the endosomal calcium channel mucolipin-1, as well as FYCO1, the AP1 adaptor, and its partner Gadkin. We conclude that endo-lysosomes in nonspecialized cells can acquire secretory functions elicited by cyclodextrin and that this pathway is responsible for the decrease in cholesterol storage in Niemann-Pick C cells.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Vacca F,Vossio S,Mercier V,Moreau D,Johnson S,Scott CC,Montoya JP,Moniatte M,Gruenberg Jdoi
10.1194/jlr.M089979subject
Has Abstractpub_date
2019-04-01 00:00:00pages
832-843issue
4eissn
0022-2275issn
1539-7262pii
jlr.M089979journal_volume
60pub_type
杂志文章abstract：:HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1194/jlr.M400052-JLR200
更新日期：2005-03-01 00:00:00
abstract：:Macrophages contain a neutral cholesteryl ester hydrolase that can be activated by cAMP-dependent protein kinase. Immunological studies strongly suggest that hormone-sensitive lipase (HSL) is probably responsible for the cholesteryl ester hydrolase activity in macrophages; however, due to the very low level of express...
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 positive effect of all-trans retinoic acid (ATRA) on white adipose tissue (WAT) oxidative and thermogenic capacity has been described and linked to an in vivo fat-lowering effect of ATRA in mice. However, little is known about the effects of ATRA on mitochondria in white fat. Our objective has been to characterize t...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M053652
更新日期：2015-06-01 00:00:00
abstract：:Lymph chylomicrons of different sizes are known to be cleared at different rates, but the underlying mechanism for this effect has not been resolved. To investigate the differences in clearance rates between small and large particles, chylomicron-like lipid emulsions labeled with radioactive triolein and cholesteryl o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Conventional ideas concerning the unidirectional movement of triacylglycerol from intestinal lumen to lymph with sn-2-monoacylglycerol being the major glyceride-glycerol precursor were challenged by our finding that steady state specific activities of radiolabeled triacylglycerol (glyceryl moiety) in the intestinal mu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:Semi-purified diets supplemented with either a high linoleate (n-6) (safflower) oil or a high alpha-linolenate (n-3) (perilla) oil were fed to mouse mothers and their offspring through 6 weeks of age. The proportions of n-3 and n-6 highly unsaturated fatty acids in brain phospholipids reflected the n-3/n-6 balance of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:We used [2-13C1]glycerol to characterize very low density lipoprotein (VLDL)-triglyceride kinetics and intrahepatic glycerol metabolism in normal men (n = 4) after alcohol (EtOH) ingestion. [2-13C1]glycerol was infused before and after the consumption of 48 g EtOH or a placebo. Three additional subjects also received ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 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：:Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200312-jlr200
更新日期：2003-01-01 00:00:00
abstract：:Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Fungal lipases and human pancreatic lipase (hPL) share a common tertiary structure termed the alpha/beta hydrolase fold. In contrast, the region C-terminal to the common tertiary structure does not share any common structural features with fungal lipases, leading to the hypothesis that the divergent C-terminal domain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Very few studies have investigated the interrelations between proprotein convertase subtilisin/kexin type 9 (PCSK9) metabolism, cholesterol synthesis, and cholesterol absorption. We aimed to address this issue in a large clinical trial of 245 patients with hypercholesterolemia. Serum lipids, PCSK9, lathosterol (choles...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P088583
更新日期：2019-01-01 00:00:00
abstract：:A novel water-soluble polysaccharide fraction, CME-1, with a molecular mass of 27.6 kDa and containing mannose and galactose in a respective ratio of 4:6, was prepared from Cordyceps sinensis mycelia and identified by NMR and GC-MS. In the current study, we examined whether CME-1 has anti-inflammatory effects in RAW26...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M011015
更新日期：2011-03-01 00:00:00
abstract：:Serine palmitoyltransferase [EC 2.3.1.50] initiates the biosynthesis of sphingolipids by catalyzing the condensation of a fatty acyl-CoA with serine to yield the committed intermediate 3-ketosphinganine or one of its homologues. The presence of serine palmitoyltransferase in aorta was established under optimal assay c...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:The common bile acids of rat bile (chenodeoxycholic, hyodeoxycholic, cholic, alpha-muricholic, and beta-muricholic acids) are completely separated by a new thin-layer chromatographic system. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-05-01 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：:In addition to its role in the uptake of apolipoprotein B (apoB)-containing lipoproteins, apoE promotes hepatic very low density lipoprotein-triglyceride (VLDL-TG) production in animal models. However, it is not known if apoE increases the amount of TG per VLDL particle or the number of VLDL particles secreted. VLDL-a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:Our previous studies have demonstrated the activity of oncostatin M (OM) in stimulating the transcription of the human LDL receptor (LDLR) gene in HepG2 cells through a sterol-independent regulatory mechanism. The current studies were designed to determine whether this in vitro property of OM could be recapitulated in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400425-JLR200
更新日期：2005-06-01 00:00:00
abstract：:The lipids of rat milk, the contents of 9-- 10-day-old rat stomach and intestine, lymph, plasma, and liver were quantitated and their fatty acids were analyzed. Rat milk consists of 97% triacylglycerols, of which 35% of the fatty acids are of medium chain length (C8-C12). However, stomach triacylglycerols show a 25% r...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-05-01 00:00:00
abstract：:Circulating concentrations of mevalonic acid (MVA) change in parallel with, and may be used as a marker of cholesterol biosynthesis. Plasma MVA levels have been quantified using a sensitive and specific capillary gas chromatography-electron capture mass spectrometric assay. The detection limit for MVA in plasma is 100...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-06-01 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：:Guinea pig gallbladder bile contains chenodeoxycholic acid (62 +/- 5%), ursodeoxycholic acid (8 +/- 5%), and 7-ketolithocholic acid (30 +/- 5%). All three bile acids became labeled to the same specific activity within 30 min after [3H]cholesterol was injected into bile fistula guinea pigs. When a mixture of [3H]ursode...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Dysbetalipoproteinemia, an uncommon but highly atherogenic mixed hyperlipidemia due to the accumulation of remnants of triglyceride-rich lipoproteins, is characterized by cholesterol-enriched VLDL that migrates in the beta-position on agarose gels. The demonstration of a broad beta-band on agarose gel electrophoresis ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.d200013-jlr200
更新日期：2003-01-01 00:00:00
abstract：:A preparation of cerebral microvessels was used to demonstrate the presence of lipoprotein lipase and acid lipase activity in the microvasculature of rabbit brain. Microvessels, consisting predominantly of capillaries, small arterioles, and venules, were islated from rabbit brain. Homogenates were assayed for lipolyti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-05-01 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：:Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14C] 24:6n-3 was 2.7 times higher than for [1-14C]22:6n-3, whereas [1-14C]22:6n-3 was incorporat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300223-JLR200
更新日期：2003-10-01 00:00:00
abstract：:Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M057570
更新日期：2015-09-01 00:00:00
abstract：:Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs throug...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089714
更新日期：2019-04-01 00:00:00
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：:To obtain a panel of monoclonal antibodies (MAbs) to study the folding and conformation of the low density lipoprotein receptor (LDLr), we have generated hybridomas from LDLr-deficient mice that had been immunized with the extracellular domain of the human LDLr. The 12 MAbs were specific for the ligand binding domain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600130-JLR200
更新日期：2006-07-01 00:00:00
