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/PS-NA has the acid beta-glucosidase (GCase) V394L/V394L (4L) point mutation combined with hypomorphic ( approximately 6% wild-type) expression of the mouse prosaposin transgene (PS-NA). The hGCase/4L/PS-NA had exclusive liver expression of hGCase controlled by doxycycline (DOX). In the absence of DOX, hGCase was secreted from liver at levels of approximately 120 microg/ml serum with only approximately 8% of full activity, following exposure to pH 7.4 in serum. The hGCase activity and protein were detected in cells of the liver (massive), lung, and spleen, but not the brain. The visceral tissue storage cells and glucosylceramide (GC) accumulation in hGCase/4L/PS-NA were decreased from that in 4L/PS-NA mice. Turning off hGCase expression with dietary DOX led to reaccumulation of storage cells and of GC in liver, lung, and spleen, and macrophage activation in those tissues. This study demonstrates that conditionally expressed hGCase supplemented the existing mutant mouse GCase to control visceral substrate accumulation in vivo.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Sun Y,Quinn B,Xu YH,Leonova T,Witte DP,Grabowski GAdoi
10.1194/jlr.M600239-JLR200subject
Has Abstractpub_date
2006-10-01 00:00:00pages
2161-70issue
10eissn
0022-2275issn
1539-7262pii
M600239-JLR200journal_volume
47pub_type
杂志文章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::The chemical and biochemical properties of cholesterol-enriched and cholesterol-poor chylomicrons from rat lymph have been compared. The enriched particles, prepared from cholesterol-containing lipid dispersions, passed into the duodenum, had four to ten times the cholesteryl ester content of the control chylomicrons ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1978-08-01 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::In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, nongenomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M085191
更新日期:2018-12-01 00:00:00
abstract::Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endolysosomal sys...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.RA119000516
更新日期:2020-07-01 00:00:00
abstract::ZR-78 and ZR-82 cells are two peroxisomal-deficient Chinese hamster ovary (CHO) cell mutants. These cells lack normal peroxisomes and show reduced levels of plasmalogen synthesis and other peroxisomal functions attributed to the deficiency of peroxisomal matrix enzymes. As we have recently identified two HMG-CoA reduc...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Apolipoprotein A-I (apoA-I) induces the translocation of newly synthesized cholesterol as well as caveolin-1 to the cytosolic lipid-protein particle (CLPP) fraction in astrocytes before its appearance in high density lipoprotein generated in the medium (Ito, J., Y. Nagayasu, K. Kato, R. Sato, and S. Yokoyama. 2002. Ap...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M400222-JLR200
更新日期:2004-12-01 00:00:00
abstract::Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cho...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M054882
更新日期:2015-07-01 00:00:00
abstract::Total serum free fatty acids (FFAt) levels provide an important measure of the physiologic state. Most of the FFA in serum is bound to albumin; a small portion, however, is unbound. This study presents the first measurements of serum unbound free fatty acid (FFAu) concentrations. These measurements were made possible ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::The Niemann-Pick C1 (NPC1) protein regulates cholesterol transport from late endosomes-lysosomes to other intracellular compartments. In this article, cholesterol transport to caveolin-1 and caveolin-2 containing compartments, such as the trans-Golgi network (TGN) and plasma membrane caveolae, was examined in normal (...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Naturally occurring derivatives of arachidonic acid are potent agonists for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and block cancer cell proliferation through the induction of apoptosis. We have previously reported that induction of apoptosis using cyclopentenone pros...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.m200224-jlr200
更新日期:2002-11-01 00:00:00
abstract::Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyt...
journal_title:Journal of lipid research
pub_type: 杂志文章,随机对照试验
doi:10.1194/jlr.P093013
更新日期:2019-06-01 00:00:00
abstract::Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity and genetic defects of lysosomal acid lipase (LAL). The strikingly more severe course of WD is caused by genetic defects of LAL that leave no residual enzymatic activity. Mutations a...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Here, we present an improved method for sensitive profiling of lipids in a single high-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry experiment. The approach consists of i) sensitive isocratic elution, which takes advantage of C18 column material that is resistan...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M700060-JLR200
更新日期:2007-09-01 00:00:00
abstract::Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual clas...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.RA120000950
更新日期:2020-07-09 00:00:00
abstract::Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and en...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R900010-JLR200
更新日期:2009-10-01 00:00:00
abstract::Studies were carried out to determine whether apolipoprotein (apo) A-II, like apoA-I, can recruit phospholipid and cholesterol from cell membranes, thereby forming nascent apoA-II-specific HDL. ApoA-II and apoA-I were purified from plasma and each was incubated with CHO cells at a concentration of 10 micrograms/ml. Li...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 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::Previous studies have reported both positive and negative effects of culture of islets at high glucose concentrations on regulated insulin secretion. Here, we have reexamined this question in mouse islets and determined the role of changes in lipid synthesis in the effects of glucose. Glucose-stimulated insulin secret...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M700533-JLR200
更新日期:2008-04-01 00:00:00
abstract::Glycolipids were isolated from the brain of a patient with a myoclonic variant of late infantile amaurotic idiocy. There was an abnormal glycolipid pattern in gray and white matter. The observed high concentration of gangliosides was due to a uniform accumulation of all four major gangliosides and was not limited to o...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1970-05-01 00:00:00
abstract::To consider possible interaction of the phospholipid membrane with calcium ions, crystal structures of calcium dl-alpha- and beta-glycerophosphates (alpha- and beta-CaGs, respectively) were investigated by X-ray diffraction methods. After many attempts, relatively large single crystals of beta-CaG were prepared from t...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Three colipases were purified from pancreas of two birds (ostrich and turkey) and one mammal (dromedary). After acidic and/or heat treatment and precipitation by sulfate ammonium and then ethanol, cofactors were purified by Sephadex G-50 gel filtration followed by ion-exchange chromatography first on Mono S and then o...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600242-JLR200
更新日期:2006-12-01 00:00:00
abstract::The effect of a single glucose feeding upon the net inflow and outflow transport of plasma free fatty acids (FFA) has been studied in 75 unanesthetized rats. The animals were fasted for 22 +/- 2 hr; then 50 rats were refed 2 ml of 50% glucose by gastric intubation. At 0, 10-15, and 30-35 min after glucose refeeding, t...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1969-01-01 00:00:00
abstract::Different batches of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) had varying amounts of contaminants which appeared to affect systematic biological studies. This contaminant was separated by silica gel column chromatography followed by high performance liquid chromatography and identified as 1,3-distearoyl-glyce...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1980-01-01 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::ATP-citrate lyase (ACL) is a key lipogenic enzyme that converts citrate in the cytoplasm to acetyl-CoA, the initial precursor that yields malonyl-CoA for fatty acid biosynthesis. As cytosolic citrate is derived from the tricarboxylic acid cycle in the mitochondrion, ACL catalyzes a critical reaction linking cellular g...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M003335
更新日期:2010-09-01 00:00:00
abstract::Biliary lipids (bile salts, phospholipids, cholesterol, plant sterols) were determined in 89 vertebrate species (cartilaginous and bony fish, reptiles, birds, and mammals), and individual phospholipid classes were measured in 35 species. All samples contained conjugated bile salts (C(27) bile alcohol sulfates and/or N...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500178-JLR200
更新日期:2005-10-01 00:00:00
abstract::In this work, we investigated the impact of testosterone deficiency and cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg) littermates were studied 4 weeks after bilateral orchidectomy or sham operation. Castrate...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600135-JLR200
更新日期:2006-07-01 00:00:00
abstract::Rab GTPases require special machinery for protein prenylation, which include Rab escort protein (REP) and Rab geranylgeranyl transferase (RGGT). The current model of Rab geranylgeranylation proposes that REP binds Rab and presents it to RGGT. After geranylgeranylation of Rab C-terminal cysteines, REP delivers the pren...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R500017-JLR200
更新日期:2006-03-01 00:00:00
abstract::The enzymic incorporation of choline-1,2-(14)C from CDP-choline-1,2-(14)C into phosphatidylcholine by spinach leaf preparations was characterized. The enzyme catalyzing the incorporation, choline phosphotransferase, had a pH optimum of about 8.0 and required either Mn(2+) or Mg(2+) as cofactor. The saturation concentr...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-07-01 00:00:00