Abstract：
:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. More than half of older AML patients fail to respond to cytotoxic chemotherapy, and most responders relapse with drug-resistant disease. Failure to achieve complete remission can be partly attributed to the drug resistance advantage of AML blasts that frequently express P-glycoprotein (P-gp), an ATP-binding cassette transporter. Our previous work showed that elevated acid ceramidase (AC) levels in AML contribute to blast survival. Here, we investigated P-gp expression levels in AML relative to AC. Using parental HL-60 cells and drug-resistant derivatives as our model, we found that P-gp expression and efflux activity were highly upregulated in resistant derivatives. AC overexpression in HL-60 conferred resistance to the AML chemotherapeutic drugs, cytarabine, mitoxantrone, and daunorubicin, and was linked to P-gp upregulation. Furthermore, targeting AC through pharmacologic or genetic approaches decreased P-gp levels and increased sensitivity to chemotherapeutic drugs. Mechanistically, AC overexpression increased NF-κB activation whereas NF-kB inhibitors reduced P-gp levels, indicating that the NF-kappaB pathway contributes to AC-mediated modulation of P-gp expression. Hence, our data support an important role for AC in drug resistance as well as survival and suggest that sphingolipid targeting approaches may also impact drug resistance in AML.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Tan SF,Dunton W,Liu X,Fox TE,Morad SAF,Desai D,Doi K,Conaway MR,Amin S,Claxton DF,Wang HG,Kester M,Cabot MC,Feith DJ,Loughran TP Jrdoi
10.1194/jlr.M091876subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1078-1086issue
6eissn
0022-2275issn
1539-7262pii
jlr.M091876journal_volume
60pub_type
杂志文章abstract：:In mammals, vitamin A is primarily stored as retinyl esters in hepatic stellate cells under normal dietary intake of the vitamin. Previously, extrahepatic vitamin A-storing stellate cells have only been identified in animals maintained on a vitamin A-rich diet, and it has not been known whether these cells play a role...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：:Bile acids labeled with 3H on the sterol nucleus lose a substantial fraction of label during enterohepatic cycling and conversion to secondary bile acids. We tested the isotopic stability of a side-chain 3H label, [22,23-3H]cholic acid in humans. The 3H-labeled compound was administered simultaneously with [24-14C]cho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 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 determined the effect of storage at -70 degrees C on the determination of plasma high density lipoprotein (HDL)-cholesterol. Plasma from 106 subjects was stored for 1, 6, and 12 months, then treated with heparin and MnCl2 to remove other lipoproteins, and HDL-cholesterol was measured. The mean HDL-cholesterol level...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Incubation of 125I-labeled very low density lipoprotein (VLDL) with lipoprotein lipase-rich (postheparin) plasma obtained from intact or supradiaphragmatic rats resulted in the transfer of more than 80% of apoprotein C from VLDL to high density lipoprotein (HDL), whereas apoprotein B was associated with lipoprotein of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300233-JLR200
更新日期：2003-12-01 00:00:00
abstract：:Placental fatty acid transport and metabolism are important for proper growth and development of the feto-placental unit. The nuclear receptors, liver X receptors alpha and beta (LXRalpha and LXRbeta), are key regulators of lipid metabolism in many tissues, but little is known about their role in fatty acid transport ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M004978
更新日期：2010-07-01 00:00:00
abstract：:The chromatographic behavior of 1,2-, 1,3-, 1,4-, and 1,12-long-chain alkane diols and 1-O-alkylglycerols and their derivatives has been compared. Thin-layer chromatography on Silica Gel G gives poor separations of the 1,2-, 1,3-, and 1,4-alkane diols, O-alkylglycerols, and some of their isopropylidene derivatives. Ho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-09-01 00:00:00
abstract：:LY295427, (3 alpha,4 alpha,5 alpha)-4-(2-propenylcholestan-3-ol), acts through an unknown mechanism to derepress the transcription of the low density lipoprotein (LDL) receptor in the presence of 25-hydroxycholesterol (25-OH chol). Preincubation with LY295427 in Chinese hamster ovary (CHO) cells increased uptake of 25...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Monolayers of Caco-2 cells, a human enterocyte cell line, were incubated with [1-14C]15-hydroxyeicosatetraenoic acid (15-HETE), a lipid mediator of inflammation, and [1-14C]arachidonic acid. Both fatty acids were taken up readily and metabolized by Caco-2 cells. [1-14C]Arachidonic acid was directly esterified in cellu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Plasma lipoprotein lipase (LPL) activity correlates with high density lipoprotein (HDL) cholesterol levels in humans. However, in several mouse models created either through transgenesis or targeted inactivation of LPL, no significant changes in HDL cholesterol values have been evident. One possible explanation for th...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P044982
更新日期：2014-02-01 00:00:00
abstract：:A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and dehydroepiandrosterone (DHEA-S) in rat brain. Using a solid-phase extraction recycling protocol, the results show that little or no PREG-S and DHEA-S (<1 pmol/g) is pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400244-JLR200
更新日期：2004-12-01 00:00:00
abstract：:Described herein are the chemical syntheses of a number of deuterated derivatives of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one. These include the [2,2,3 alpha,4,4,7,7,9 alpha,16,16-2H10]-, [7 alpha,9 alpha,16,16-2H4]-, [7,7,9 alpha,16,16-2H5]-, and [2,2,3 alpha,4,4-2H5]-analogs of the delta 8(14)-15-ketosterol. Also i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 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 role of plasma free fatty acids (FFA) in the transport of fatty acids from host tissues to Ehrlich ascites carcinoma in mice was studied. [9,10-(3)H] Palmitate complexed to mouse serum (albumin) was injected either intraperitoneally or intravenously into unanesthetized tumor-bearing mice. The incorporation of radi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1974-07-01 00:00:00
abstract：:Biliary cholesterol secretion is ordinarily tightly coupled to phosphatidylcholine (PC) secretion. Bile PCs are distinct in composition and predominantly composed of molecular species with 16:0 in the sn-1 position and 18:2 and 18:1 in the sn-2 position. In an attempt to acutely change the composition of biliary PCs a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M090548
更新日期：2019-03-01 00:00:00
abstract：:Lipid droplet proteins (LDPs) coat the surface of triglyceride-rich lipid droplets and regulate their formation and lipolysis. We profiled hepatic LDP expression in fatty liver dystrophic (fld) mice, a unique model of neonatal hepatic steatosis that predictably resolves between postnatal day 14 (P14) and P17. Western ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M000976
更新日期：2010-03-01 00:00:00
abstract：:The apoE gene exhibits two common polymorphisms that have been associated with both coronary artery disease and Alzheimer's disease. The polymorphisms create the three allelic isoforms E2, E3, and E4 which are encoded by Cys;-Cys, Cys;-Arg, and Arg;-Arg at amino acid positions 112 and 158, respectively. Numerous metho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:Lipid transfer inhibitor protein (LTIP) is a regulator of cholesteryl ester transfer protein (CETP) function. Factors affecting plasma LTIP levels are poorly understood. In humans, plasma LTIP is elevated in hypercholesterolemia. To define possible mechanisms by which hyperlipidemia modifies LTIP, we investigated the ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800429-JLR200
更新日期：2009-04-01 00:00:00
abstract：:This review presents an overview of mammalian phospholipid synthesis and the cellular locations of the biochemical activities that produce membrane lipid molecular species. The generalized endoplasmic reticulum compartment is a central site for membrane lipid biogenesis, and examples of the emerging relationships betw...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800049-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Apolipoprotein (apo) E, via its receptor binding domain contained in residues 140-150, mediates hepatic and peripheral tissue binding of cholesterol-rich lipoproteins. Previously, we reported that a synthetic peptide representing a linear tandem repeat of amino acids 141-155, the 141-155 dimer, binds the low density l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Recent studies demonstrate that HDL's ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear....
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M059089
更新日期：2015-08-01 00:00:00
abstract：:Solid-phase extraction (SPE) methods are easy, rapid, and reliable. Their growing popularity is in part due to their operational simplicity and cost reduction in solvents, and partly because they are easier to automate. Sphingolipids are implicated in various cellular events such as growth, differentiation, and apopto...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-09-01 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：:Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has previously been shown to be able to decrease porcine subcutaneous (SC) adipose tissue levels while increasing the count of intramuscular (IM) adipose tissue in vivo. However, the underlying mechanisms through which it acts are poorly understood...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600525-JLR200
更新日期：2007-08-01 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：:Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, specifically decreased triglyceride (TG) accumulation in primary human adipocytes...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300001-JLR200
更新日期：2003-07-01 00:00:00
