Abstract：
:ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that the transcriptional upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts HDL function. Employing the small molecule triacetyl-3-hydroxyphenyladenosine (IMM-H007), we determined how the attenuation of ABCA1 protein degradation affects HDL cholesterol efflux capacity, RCT, and atherosclerotic lesion formation. Pulse-chase analysis revealed that IMM-H007 inhibits ABCA1 degradation and facilitates its cell-surface localization in macrophages, and additional studies in macrophages showed that IMM-H007 thereby promotes cholesterol efflux. IMM-H007 treatment of Paigen diet-fed mice caused an increase in circulating HDL level, it increased the cholesterol efflux capacity of HDL, and it enhanced in vivo RCT from macrophages to the plasma, liver, and feces. Furthermore, ABCA1 degradation suppression by IMM-H007 reduced atherosclerotic plaque formation in apoE(-/-) mice. Thus, via effects on both ABCA1-expressing cells and circulating HDL function, the inhibition of ABCA1 protein degradation by IMM-H007 promotes HDL cholesterol efflux capacity and RCT and attenuates atherogenesis. IMM-H007 potentially represents a lead compound for the development of agents to augment HDL function.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Huang L,Fan B,Ma A,Shaul PW,Zhu Hdoi
10.1194/jlr.M054742subject
Has Abstractpub_date
2015-05-01 00:00:00pages
986-97issue
5eissn
0022-2275issn
1539-7262pii
jlr.M054742journal_volume
56pub_type
杂志文章abstract：:Sterol-regulatory element binding protein-1c (SREBP-1c) is a transcription factor that controls lipogenesis in the liver. Hepatic SREBP-1c is nutritionally regulated, and its sustained activation causes hepatic steatosis and insulin resistance. Although regulation of SREBP-1c is known to occur at the transcriptional l...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M004234
更新日期：2010-07-01 00:00:00
abstract：:Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are r...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000991
更新日期：2020-11-01 00:00:00
abstract：:The origin of arachidonic acid (AA) found in the epidermis is not known. Two possibilities exist: either de novo synthesis within the epidermal keratinocyte, or transport of AA formed at distant tissue sites. The current study examined the ability of cultured murine and human keratinocytes to metabolize exogenously ad...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 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：:This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormon...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia-inducible lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular m...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082388
更新日期：2018-03-01 00:00:00
abstract：:In this study, we examined effects of retinol deficiency and three retinoids, all-trans-retinoic acid, 13-cis-retinoic acid, and etretin, the aromatic derivative of retinoic acid on nuclear retinoic acid receptor isoforms alpha, beta, and gamma mRNA in rat adipose tissue. Retinol deficiency caused an almost 50% decrea...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
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：:Various detergents can be used to dissolve phospholipids, resulting in very narrow 31PNMR resonances. The resonances are well resolved, allowing identification and quantitative analysis of phospholipids in a mixture. The chemical shift depends strongly on pH, reflecting changes in the state of ionization of the phosph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:Lipogenesis in vitro from acetate-1-(14)C was studied in human preputial skin and abdominal skin. Radioactive lipids were separated by column chromatography on Florisil and by thin-layer chromatography on silica gel. Radioactivity was incorporated chiefly into the triglyceride, sterol, and polar lipid fractions, while...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-09-01 00:00:00
abstract：:The genus Acinetobacter is composed of ubiquitous, generally nonpathogen environmental bacteria. Interest concerning these microorganisms has increased during the last 30 years, because some strains, belonging to the so-called A. baumannii-A. calcoaceticus complex, have been implicated in some severe pathological stat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600323-JLR200
更新日期：2007-05-01 00:00:00
abstract：:Vitamin E (α-tocopherol) is the major lipid-soluble antioxidant in many species. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway. NPC disease is characterized by massive intracellular accumulat...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M015560
更新日期：2011-07-01 00:00:00
abstract：:In the present study, the relative positions of 11 anti-apolipoprotein B monoclonal antibodies have been mapped onto the surface of human low density lipoproteins by electron microscopy. As the epitopes recognized by these antibodies have been previously located on the primary sequence of apoB, these data provide a ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:The vitamin D signal transduction system involves a series of cytochrome P450-containing sterol hydroxylases to generate and degrade the active hormone, 1α,25-dihydroxyvitamin D3, which serves as a ligand for the vitamin D receptor-mediated transcriptional gene expression described in companion articles in this review...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R031534
更新日期：2014-01-01 00:00:00
abstract：:Sphingoglycolipids (SGLs) are cell membrane constituents. As the ceramide structure influences the biological properties of the SGL, we characterized by electrospray ionization tandem mass spectrometry the molecular species of ceramides present in SGL of mouse brain. We report here for the first time the presence in m...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300331-JLR200
更新日期：2004-02-01 00:00:00
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/...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600239-JLR200
更新日期：2006-10-01 00:00:00
abstract：:Seven Z-octadecenoic acids having the double bond located in positions 6Z to 13Z were photooxidized. The resulting hydroperoxy-E-octadecenoic acids [HpOME(E)] were resolved by chiral phase-HPLC-MS, and the absolute configurations of the enantiomers were determined by gas chromatographic analysis of diastereoisomeric d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M018259
更新日期：2011-11-01 00:00:00
abstract：:The characteristics of 7 alpha-dehydroxylase, a bile acid-biotransforming enzyme, were determined using dialyzed cell extracts of Eubacterium sp. V.P.I. 12708. 7 alpha-Dehydroxylase was induced by cholic acid in this organism. Induction by cholic acid resulted in the differential synthesis of at least five new polypep...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 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：:High density lipophorin (HDLp is the main lipoprotein found in resting insect hemolymph. It has, in general, two molecules of apolipoproteins: apoLp-I (250 kDa) and apoLp-II (80 kDa) and a variable lipid content which ranges from 35% to 59% (w/w). Diacylglycerols (DG), phospholipids (PL), and hydrocarbons (HC) are the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Adiponectin, an adipocyte-derived protein, has antiatherogenic and antidiabetic effects, but how it confers the atherogenic effects is not well known. To study the antiatherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low density lipoprotein (LDL) to attenuate LDL's atherogenicit...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA120000767
更新日期：2020-11-21 00:00:00
abstract：:Absorption rates for many biologically important compounds are determined by the relative hydrophobicity of the jejunal microvillus membrane. An estimate of this parameter may be obtained by measuring the incremental change in free energy that occurs when a methylene group partitions into the bilayer form an external ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:Studies were conducted to explore vitamin A transport in the non-mammalian vertebrates, especially Pisces, Amphibia, and Reptilia, and to isolate and partially characterize piscine retinol-binding protein. Retinol-containing proteins in fresh plasma obtained from bullfrogs and a turtle exhibited similar properties to ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:HDLs have been proposed to have antiatherogenic properties because of their role in reverse cholesterol transport as lipid acceptors. To elucidate the phospholipid profile of these particles, we used electrospray ionization mass spectrometry to examine the phosphatidylcholine (PC) and sphingomyelin (SM) composition of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500011-JLR200
更新日期：2005-06-01 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：:Zonation affects liver parenchymal cell function and metabolism as well as nonparenchymal cell activation, but whether VLDL production is zonated has yet to be elucidated. Infection induces enhanced VLDL secretion by the liver. Ex vivo studies were undertaken to examine the liver heterogeneity for VLDL formation and s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500003-JLR200
更新日期：2005-05-01 00:00:00
abstract：:HDL cholesterol levels are decreased in Crohn's disease, a tumor necrosis factor-alpha (TNF-alpha)-driven chronic inflammatory condition involving the gastrointestinal tract. ATP-binding cassette transporter A1 (ABCA1), one of several liver X receptor (LXR) target genes, is a cell surface transporter that mediates the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M002410
更新日期：2010-06-01 00:00:00
abstract：:The sialic acid present in erythrocyte ghosts was estimated by methane chemical ionization mass fragmentography of the trimethylsilyl methyl glycosides. The internal standard was 3,4,6-tris-trimethylsilyl-alpha-phenyl-2-deoxy-2-acetamide-D-glucosaminide, as proposed by Yu and Ledeen (J. Lipid Res. 1970. 11: 506-516). ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-11-01 00:00:00
abstract：:LCAT plays a key role in the maturation of HDL, as evidenced by low HDL-cholesterol levels in carriers of deleterious mutations in LCAT. However, the role of LCAT in atherosclerosis is unclear. We set out to study this in a prospective study. Plasma LCAT levels, which strongly correlate with LCAT activity, were measur...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/P900038-JLR200
更新日期：2010-02-01 00:00:00
abstract：:A method has been described for the measurement of apoB concentration and specific activity in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) during metabolic studies. For measurement of specific activity, apoB was separated from other apolipoproteins and lipids by precipitation in, and subseque...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
