Abstract：
:Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Clarke CJ,Shamseddine AA,Jacob JJ,Khalife G,Burns TA,Hannun YAdoi
10.1194/jlr.M067447subject
Has Abstractpub_date
2016-05-01 00:00:00pages
868-81issue
5eissn
0022-2275issn
1539-7262pii
jlr.M067447journal_volume
57pub_type
杂志文章abstract：:This report describes the chemical synthesis of isoursocholic acid (3 beta, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) from its corresponding 3 alpha-analog. The method consists of refluxing a mixture of ursocholic acid, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 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
abstract：:The phase behavior and temperature-dependent molecular motions of three cholesteryl ethers (caproyl, myristyl, oleyl) and a cholesteryl carbonate (oleyl) were characterized. The properties of each ether were qualitatively similar to, but quantitatively different from, those of the corresponding cholesteryl ester. For ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:We have developed a procedure to quantify apolipoprotein (apo) B-100, apoB-48, and apoE in human triglyceride-rich lipoproteins. This procedure permits delipidation of small amounts of triglyceride-rich lipoproteins without appreciable losses, and quantification of these apolipoproteins in samples containing as little...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:The biosynthesis of prostaglandins by isolated rat adrenocortical cells has been studied by determinations of products formed during incubations with labeled arachidonic acid and by radioimmunoassays. Analysis by thin-layer chromatographic separation of silicic acid column fractions indicated that PGE2, PGA2, (B2) and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:The essential fatty acid DHA (22:6, omega-3 or n-3) is enriched in and required for the membrane biogenesis and function of photoreceptor cells (PRC), synapses, mitochondria, etc. of the CNS. PRC DHA becomes an acyl chain at the sn-2 of phosphatidylcholine (PC), amounting to more than 50% of the PRC outer segment phos...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.TR120001137
更新日期：2020-10-26 00:00:00
abstract：:Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 ex...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034710
更新日期：2013-04-01 00:00:00
abstract：:The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations wer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P600002-JLR200
更新日期：2006-12-01 00:00:00
abstract：:Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been relat...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R900011-JLR200
更新日期：2009-09-01 00:00:00
abstract：:The role of lipid transfer proteins during plasma membrane biogenesis was explored. Developing amphibia embryos were used because during their growth an active plasma membrane biosynthesis occurs together with negligible mitochondrial and endoplasmic reticulum proliferation. Sonicated vesicles, containing 14C-labeled ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Several lipoprotein lipase (LPL) gene polymorphisms have been found associated with fasting lipid levels, but their impact on coronary heart disease (CHD) is less clearly established. We investigated associations of LPL polymorphisms (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) and facilitates the efflux of unesterified cholesterol. SR-BI expression in macrophages presumably plays a role in atherosclerosis. The role of SR-BI for selective CE uptake and cholesterol efflux in macrophages was...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600136-JLR200
更新日期：2006-11-01 00:00:00
abstract：:Recently we evaluated an isotope ratio method (IRM) for measurement of cholesterol absorption in 14 patients (15 experiments) hospitalized in the metabolic ward by comparing it to simultaneous measurements with a fecal radioactivity method (FRM) and found good to excellent agreement between two procedures (Samuel, P.,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-03-01 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：:Initiation of atherosclerosis is characterized by accumulation of aggregates of small lipid droplets and vesicles in the extracellular matrix of the arterial intima. The droplets and vesicles have features that suggest that they are formed from modified plasma-derived low density lipoprotein (LDL) particles. A variety...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：2000-11-01 00:00:00
abstract：:Each abdominal fat depot, such as mesenteric or epididymal, differently contributes to the development of insulin resistance. The aim of this study was to identify the genetic regions that contribute to fat accumulation in epididymal/mesenteric fat and to examine whether or not the genetic regions that affect glucose ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M009563
更新日期：2010-12-01 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：:Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:Paraoxonases (PONs) are a small family of antioxidant enzymes whose antiatherogenic activity is well known. The aim of the present study was the evaluation of the effects of moderate aerobic training on their expression using a rat model. In order to discriminate between PON1 and PON3 enzymatic activity, we took advan...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800493-JLR200
更新日期：2009-10-01 00:00:00
abstract：:Most mammalian neoplasms have a defect in ether lipid content manifested by the presence of abnormally large quantities of 0-alkyl glyceryl ethers, in contrast to normal tissues in which the alk-1-enyl structure predominates. These lipids are for the most part structural. The manner in which tumor cell plasma membrane...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073882
更新日期：2017-07-01 00:00:00
abstract：:The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by nor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximate...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800089-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Tissue-specific regulation of LPL has been widely studied in rats. Previous studies reported that in vivo administration of adrenaline and acute stress cause an increase in plasma LPL activity coinciding with a decrease in white adipose tissue (WAT) LPL activity. We studied the speed of LPL activity changes during 30 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600487-JLR200
更新日期：2007-04-01 00:00:00
abstract：:Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. W...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The time course of the clearance from the blood and the tissue localization of [14C]L-glucosylceramide, a nonmetabolizable enantiomorph of D-glucosylceramide that accumulates in Gaucher's disease, has been determined. 14C-labeled L-glucosylceramide injected intravenously in the form of micelles or liposomes is rapidly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:Conditions under which apolipoprotein (apo) A-I dissociates from human high density lipoproteins (HDL) during incubation in vitro have been investigated. Dissociation of apoA-I was demonstrated by non-denaturing gradient gel electrophoresis followed by immunoblotting for apoA-I and by size-exclusion chromatography. It...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Percent cholesterol absorption was measured in 94 normal subjects aged 17- 80 years while consuming diets generally low in cholesterol (mean intake = 226 +/- 126 mg/day). A new dual stable isotope method was used where a cholesterol tracer containing 6 extra mass units was given intravenously and another tracer with 5...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-02-01 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：:A rapid isocratic method for determining the total phosphatidylcholine and disaturated phosphatidylcholine levels in lung surfactant preparations by high performance liquid chromatography (HPLC) is described. The analysis was performed on a 3.9 x 300 mm mu-Porasil column with detection by refractive index. The lipids ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
