Abstract：
:Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of FXRα1 and FXRα2 in patients with hepatocellular carcinoma. In this study, we demonstrate that FXRα1 and FXRα2 regulate human BSEP through two distinct FXR responsive elements (FXRE): IR1a and IR1b. As the predominant regulator, FXRα2 potently transactivated human BSEP through IR1a, while FXRα1 weakly transactivated human BSEP through a newly identified IR1b. Relative expression of FXRα1 and FXRα2 affected human BSEP expression in vitro and in vivo. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the binding and recruitment of FXRα1 and FXRα2 to IR1b and IR1a. Sequence analysis concluded that IR1b was completely conserved among species, whereas IR1a exhibited apparent differences across species. Sequence variations in IR1a were responsible for the observed species difference in BSEP transactivation by FXRα1 and FXRα2. In conclusion, FXR regulates BSEP in an isoform-dependent and species-specific manner through two distinct FXREs, and alteration of relative FXR isoform expression may be a potential mechanism for FXR to precisely regulate human BSEP in response to various physiological and pathological conditions.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Song X,Chen Y,Valanejad L,Kaimal R,Yan B,Stoner M,Deng Rdoi
10.1194/jlr.M038323subject
Has Abstractpub_date
2013-11-01 00:00:00pages
3030-44issue
11eissn
0022-2275issn
1539-7262pii
jlr.M038323journal_volume
54pub_type
杂志文章abstract：:Treatment of native human Lp(a) under nondenaturing conditions with dithiothreitol yielded both a lipoprotein particle and a lipid-free protein component that could be separated by either ultracentrifugation at d 1.063 g/ml or heparin-Sepharose chromatography. The protein component only showed antigenicity against ant...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 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：:3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) are metabolized into chenodeoxycholic acid and cholic acid, respectively, through oxidation and cleavage of the terminal three carbons of the side chain. The present study was desig...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-02-01 00:00:00
abstract：:We investigated the role of caveolae in uptake and intracellular trafficking of long chain fatty acids (LCFA) in HepG2 human hepatoma cells. The uptake of [(3)H]oleic acid and [(3)H]stearic acid into HepG2 cells was measured by radioactive assays and internalization of the non-metabolizable fluorescent fatty acid 12-(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100404-jlr200
更新日期：2002-09-01 00:00:00
abstract：:Human apolipoprotein C-I (apoC-I) is an exchangeable apolipoprotein that binds to lipoprotein particles in vivo. In this study, we employed a LC-MS/MS assay to demonstrate that residues 38-51 of apoC-I are significantly protected from proteolysis in the presence of 1,2-dimyristoyl-3-sn-glycero-phosphocholine (DMPC). T...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800529-JLR200
更新日期：2009-07-01 00:00:00
abstract：:Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium ethylenediaminetetraaceti...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-03-01 00:00:00
abstract：:Characterization of the chemical form and stereo-specificity of the fatty acid derivatives of arachidonic and linoleic acid in psoriatic epidermis is needed to define the enzymatic origin of these compounds and their possible role in pathogenesis. In an analysis of psoriatic skin scales, both free and esterified 13-hy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Achilles tendon xanthomas are associated with increased cardiovascular risk in patients with familial hypercholesterolemia (FH). Oxidized low density lipoprotein (OxLDL), the antibodies against OxLDL, and the LDL-associated phospholipase A(2) (Lp-PLA(2)) may play important roles in atherogenesis. We investigated the p...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600109-JLR200
更新日期：2006-10-01 00:00:00
abstract：:Serum paraoxonase (PON1) is a HDL-associated enzyme exhibiting potentially antiatherogenic properties. Here, we examined the common PON1-192R/Q human polymorphism. Despite numerous studies, the effect of this polymorphism on the antiatherogenic potential of PON1 is yet unresolved. Our structural model suggests that am...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600297-JLR200
更新日期：2006-11-01 00:00:00
abstract：:This paper presents a case of typical hyperlipoproteinemia type I in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein B-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of n...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:We have previously demonstrated the potential usefulness of capillary columns coated with a high temperature polarizable phenylmethylsilicone liquid phase in plasma lipid profiling (Kuksis, A., J.J. Myher, and P. Sandra. 1990. J. Chromatogr. 500: 427-441). The present study reports improved operating conditions along ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:The direct effect of apolipoprotein (apo) E on cholesteryl ester transfer protein (CETP) activity was studied using lipoproteins from a subject with apoE deficiency (Atherosclerosis. 1991. 88: 15-20) as a model system. The transfer of cholesteryl ester (CE) from discoidal bilayer particles (DBP) to very low density li...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Cerebrosides containing either threo- or erythro-[3-3-H]sphingosine were synthesized by a new procedure. Glucopyranosyl or galactopyranosyl ceramides were converted to their 3-keto derivatives with 2,3-dichloro-5,6-dicyanobenzoquinone and reduced with 3-H-labeled sodium borohydride. The resulting tritiated cerebroside...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
abstract：:Insulin resistance (IR) is associated with elevated plasma levels of triglyceride-rich lipoproteins (TRLs) of intestinal origin. However, the mechanisms underlying the overaccumulation of apolipoprotein (apo)B-48-containing TRLs in individuals with IR are not yet fully understood. This study examined the relationships...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M040071
更新日期：2014-01-01 00:00:00
abstract：:Using [13C]-tracers and direct fetal doses, we show for the first time that the fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion. Pregnant female baboons consumed a diet free of long chain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 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：: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：:We have previously observed that the Ya subunit-containing glutathione (GSH) S-transferases from rat liver exhibit a common high affinity binding site for lithocholic acid, bilirubin, and sulfobromophthalein (BSP) (1984. J. Lipid Res. 25: 1177-1183). Subsequently we found that cholic acid and its amidates bound to a s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:Over the past several years, considerable progress has been made in the development of gene therapy as a therapeutic strategy for a variety of inherited metabolic diseases, including neuropathic lysosomal storage disorders (LSDs). The premise of gene therapy for this group of diseases is borne of findings that genetic...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R047175
更新日期：2014-09-01 00:00:00
abstract：:Bile salts of the coelacanth, Latimeria chalumnae, Smith, have been analyzed and shown to have three bile alcohols, latimerol, 5 alpha-cyprinol, and 5 alpha-cholestane-3 beta, 7 alpha,-12 alpha,25,26-pentol, two C24 bile acids, chenodeoxycholic acid and cholic acid, one C26 bile acid, probably 3 beta, 7 alpha, 12 alph...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-12-01 00:00:00
abstract：:Recent studies suggest: that the epidermis and pilosebaceous epithelium are important sites of de novo sterol synthesis, and that the rate of cutaneous cholesterol synthesis does not change with alterations in circulating sterol levels. Since cutaneous sterols may be important for permeability barrier function, we stu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:Thermal and lyotropic phase behavior was studied by X-ray diffraction and differential scanning calorimetry for a diether phosphonolipid analog (DEPN-8) of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine (DPPC). DEPN-8 differs in an ether, rather than an ester, bond at the acyl chain-back...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Although the synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, particularly under pathophysiological conditions, is difficult, although not impossible. Herein, we developed and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033837
更新日期：2013-04-01 00:00:00
abstract：:13C-NMR spectroscopy was used to examine the effect of side chain length on the ionization properties and transmembrane transport rate of 3 alpha,7 alpha-dihydroxy bile acids. When solubilized in taurocholate micelles, [23-13C]nor-chenodeoxycholic acid (nor-CDCA) had a pKa of 6.1, similar to that of CDCA (pKa 6.2), it...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who h...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P023994
更新日期：2012-05-01 00:00:00
abstract：:Lipids are used as cellular building blocks and condensed energy stores and also act as signaling molecules. The glycerolipid/ fatty acid cycle, encompassing lipolysis and lipogenesis, generates many lipid signals. Reliable procedures are not available for measuring activities of several lipolytic enzymes for the purp...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D058438
更新日期：2016-01-01 00:00:00
abstract：:Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity and the regulation of autophagy is cell type specific. Despite adverse consequences of obesity on cardiac structure and function, the contribution of altered cardiac autophagy in response to fatt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M055152
更新日期：2015-03-01 00:00:00
abstract：:To study the role of phospholipids in the lipophorin structure, they were removed by phospholipase A2 treatment. Fluorescence lifetimes and accessibility to acrylamide quenching of different diphenylhexatrienyl derivatives, which were used as analogues of the different lipid components, indicate a surface localization...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic chondrodysplasia punctata, pathological accumulation of phytanic acid results from impaired alpha-oxidation of this branched-chain fatty acid. Previous studies from this laboratory indicated that activation of phytanic acid to its CoA derivative pre...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25-50 mug/ml inhibited staurosporine-induced apoptosis in THP-1 cells...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M700100-JLR200
更新日期：2008-01-01 00:00:00
