Nuclear bile acid receptor FXR as pharmacological target: are we there yet?

Abstract:

:The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is primarily expressed in the enterohepatic system where it functions as intracellular sensor for bile acids. Ligand dependent FXR activation induces transcriptional responses to coordinately regulate bile acid, cholesterol, triglyceride and glucose metabolism, and to protect the intestinal mucosa from bacterial overgrowth and inflammatory insults. Here we discuss the latest discoveries in FXR-driven metabolic pathways with relevance to pathophysiology and novel therapeutic approaches of several conditions such as hypertriglyceridemia, type 2 diabetes, cholesterol gallstone disease, steato-hepatitis and metabolic syndrome.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Modica S,Moschetta A

doi

10.1016/j.febslet.2006.07.082

subject

Has Abstract

pub_date

2006-10-09 00:00:00

pages

5492-9

issue

23

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(06)00950-1

journal_volume

580

pub_type

杂志文章,评审
  • A novel nucleotide receptor in Xenopus activates the cAMP second messenger pathway.

    abstract::We describe a Xenopus P2Y receptor that shares only weak homology with members of the mammalian P2Y family, being most similar to human P2Y(11). When activated by nucleotide analogs, it stimulates both calcium and cAMP mobilization pathways, a feature unique, among mammalian P2Y receptors, to P2Y(11). Activity can be ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2007.10.024

    authors: Devader C,Drew CM,Geach TJ,Tabler J,Townsend-Nicholson A,Dale L

    更新日期:2007-11-13 00:00:00

  • Degradation of type IX collagen by matrix metalloproteinase 3 (stromelysin) from human rheumatoid synovial cells.

    abstract::The degradation of type IX collagen, a minor collagen in cartilage, was examined by treatment with three different types of matrix metalloproteinases (MMPs) purified from the culture medium of rheumatoid synovial cells. Neither MMP-1 (collagenase) nor MMP-2 (so-called 'gelatinase') could digest type IX collagen, but M...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(89)80586-1

    authors: Okada Y,Konomi H,Yada T,Kimata K,Nagase H

    更新日期:1989-02-27 00:00:00

  • Modulation of phosphoinositide 3-kinase activation by cholesterol level suggests a novel positive role for lipid rafts in lysophosphatidic acid signalling.

    abstract::Methyl-beta-cyclodextrin (MbetaCD) was used to explore a role for cholesterol-enriched plasma membrane microdomains in coupling lysophosphatidic acid (LPA) stimulation to phosphoinositide 3-kinase (PI3K) activation. Cholesterol depletion strongly inhibited the production of phosphatidylinositol 3,4-bisphosphate and ph...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(02)03832-2

    authors: Peres C,Yart A,Perret B,Salles JP,Raynal P

    更新日期:2003-01-16 00:00:00

  • Characterization of glucose transport system in Drosophila Kc cells.

    abstract::We have characterized the glucose transport system in the Kc cells of Drosophila melanogaster. The transporter is stereospecific and can be inhibited by both cytochalasin B and phloretin, with ki values of 4 microM and 30 microM for cytochalasin B and phloretin, respectively. Moreover, phlordzin does not affect uptake...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(93)81284-7

    authors: Wang M,Wang C

    更新日期:1993-02-15 00:00:00

  • Endogenously generated 5-hydroperoxyeicosatetraenoic acid is the preferred substrate for human leukocyte leukotriene A4 synthase activity.

    abstract::A single protein from human leukocytes possesses both 5-lipoxygenase and leukotriene A4 (LTA4) synthase activities. It has been reported that LTA4 production is more efficient when the enzyme utilizes arachidonic acid, than when 5-HPETE is exogenously supplied as substrate. In the present study, human leukocyte homoge...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(87)80675-0

    authors: Puustinen T,Scheffer MM,Samuelsson B

    更新日期:1987-06-15 00:00:00

  • Mitochondrial dysfunction and nuclear-mitochondrial shuttling of TERT are involved in cell proliferation arrest induced by G-quadruplex ligands.

    abstract::G-quadruplex ligands DODC and TMPyP4 have different binding modes to quadruplex structure and cause cell proliferation arrest. Here we showed that DODC was more efficient in cell growth inhibition than TMPyP4. Both G-quadruplex ligands induced nuclear-cytoplasmic shuttling and accumulation of TERT in mitochondria. Thi...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2013.04.010

    authors: Zhuang XY,Yao YG

    更新日期:2013-06-05 00:00:00

  • Sequence-specific [1H]NMR resonance assignments and secondary structure identification for 1- and 2-zinc finger constructs from SW15. A hydrophobic core involving four invariant residues.

    abstract::Complete [1H]NMR resonance assignments are presented for the second of the three zinc fingers from SW15 as it appears in both 1- and 2-finger constructs. Signals from finger 2 are unaffected by the presence or absence of finger 1, showing that the protein has a modular construction. The structure of finger 2 comprises...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(90)80184-k

    authors: Neuhaus D,Nakaseko Y,Nagai K,Klug A

    更新日期:1990-03-26 00:00:00

  • Visualization of protein transport along the secretory pathway using green fluorescent protein.

    abstract::We have expressed green fluorescent protein (GFP) from A. victoria in the secretory pathway of HeLa cells by fusing it to the C-terminus of a secretory protein, chromogranin B. Under normal culture conditions at 37 degrees C maturation of GFP to the fluorescent form was not detectable. However, fluorescent GFP was obs...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(95)00765-2

    authors: Kaether C,Gerdes HH

    更新日期:1995-08-07 00:00:00

  • A new intrinsic fluorescent probe for proteins. Biosynthetic incorporation of 5-hydroxytryptophan into oncomodulin.

    abstract::The tryptophan analog, 5-hydroxytryptophan (5HW), has a significant absorbance between 310-320 nm, which allows it to act as an exclusive fluorescence probe in protein mixtures containing a large number of tryptophan residues. Here for the first time a method is reported for the biosynthetic incorporation of 5HW into ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(92)81346-n

    authors: Hogue CW,Rasquinha I,Szabo AG,MacManus JP

    更新日期:1992-10-05 00:00:00

  • p21-activated protein kinase gamma-PAK in pituitary secretory granules phosphorylates prolactin.

    abstract::p21-activated protein kinase gamma-PAK phosphorylates prolactin (PRL) in rat pituitary secretory granules on Ser-177 and on the equivalent site, Ser-179, in recombinant human PRL. This is shown by comparison of phosphopeptide maps with the human PRL mutant S179D. gamma-PAK is present in rat and bovine granules as iden...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(02)02444-4

    authors: Tuazon PT,Lorenson MY,Walker AM,Traugh JA

    更新日期:2002-03-27 00:00:00

  • Molecular evolution of the calmodulin gene.

    abstract::On the basis of the intron/exon organization and the intramolecular homology of DNA sequences, I propose a novel model for genesis of the calmodulin gene. A primordial calmodulin gene consisting of 51 base pairs (17 amino acids) was subjected to three-fold duplication to create modern calmodulin with four calcium-bind...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(87)80661-0

    authors: Nojima H

    更新日期:1987-06-15 00:00:00

  • Beyond the epithelium: cadherin function in fibrous connective tissues.

    abstract::In fibrous connective tissues, fibroblasts are organized into syncytia, cellular networks that enable matrix remodeling and that are interconnected by intercellular adherens junctions (AJs). The AJs of fibroblasts are mediated by N-cadherin, a broadly expressed classical cadherin that is critically involved in develop...

    journal_title:FEBS letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.febslet.2006.12.029

    authors: El Sayegh TY,Kapus A,McCulloch CA

    更新日期:2007-01-23 00:00:00

  • Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7beta1 and dystroglycan.

    abstract::Transgenically introduced laminin (LN) alpha1 chain prevents muscular dystrophy in LNalpha2 chain deficient mice. We now report increased integrin alpha7Bbeta1D synthesis in dystrophic LNalpha2 chain deficient muscle. Yet, immunofluorescence demonstrated a reduced expression of integrin alpha7B subunit at the sarcolem...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2006.02.027

    authors: Gawlik KI,Mayer U,Blomberg K,Sonnenberg A,Ekblom P,Durbeej M

    更新日期:2006-03-20 00:00:00

  • Verification of the interdomain contact site in the inactive monomer, and the domain-swapped fold in the active dimer of Hsp33 in solution.

    abstract::Upon dimerization by oxidation, Hsp33 functions as a molecular chaperone in prokaryotes. Previously published structures of both the inactive and active species are of doubtful relevance to the solution conformations since the inactive (reduced) crystal structure was dimeric, while the active (oxidized) species was cr...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2012.01.011

    authors: Lee YS,Ryu KS,Kim SJ,Ko HS,Sim DW,Jeon YH,Kim EH,Choi WS,Won HS

    更新日期:2012-02-17 00:00:00

  • Functional identification of AtFao3, a membrane bound long chain alcohol oxidase in Arabidopsis thaliana.

    abstract::The Arabidopsis thalina genome database was searched for homologues of the Candida cloacae fao1 gene which encodes a membrane bound, flavin-containing, hydrogen peroxide generating, long chain alcohol oxidase. This gene has not been isolated from plants or animals. Four putative candidates were found in the database b...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2004.07.086

    authors: Cheng Q,Liu HT,Bombelli P,Smith A,Slabas AR

    更新日期:2004-09-10 00:00:00

  • Expression of protein kinase C isozymes in hippocampal neurones in culture.

    abstract::Several protein kinase C (PKC) isozymes were analyzed by immunoblot and immunocytochemistry in cultures of hippocampal neurones at several stages of differentiation. Our findings reveal the existence of two distinct patterns of expression. Firstly, conventional PKC isozymes alpha, beta and gamma, that are expressed at...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(95)00303-q

    authors: Tejero-Díez P,Rodríguez-Sánchez P,Díez-Guerra FJ

    更新日期:1995-04-24 00:00:00

  • An acid amidase hydrolyzing anandamide as an endogenous ligand for cannabinoid receptors.

    abstract::Anandamide loses its cannabimimetic activities upon hydrolysis to arachidonic acid and ethanolamine. So far the anandamide hydrolyzing activity widely distributed in mammalian organs has been attributed exclusively to an enzyme referred to as anandamide amidohydrolase with an optimum pH around 9. We found another enzy...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(99)00820-0

    authors: Ueda N,Yamanaka K,Terasawa Y,Yamamoto S

    更新日期:1999-07-09 00:00:00

  • TNF-alpha enhances intracellular glucocorticoid availability.

    abstract::For understanding the mechanism(s) relating inflammation to corticosteroid action, the effect of tumour necrosis factor-alpha (TNF-alpha) on 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme regulating access of 11beta-hydroxycorticosteroids to receptors, was studied in LLC-PK(1) cells. We observed ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(01)03004-6

    authors: Heiniger CD,Rochat MK,Frey FJ,Frey BM

    更新日期:2001-11-02 00:00:00

  • Crystallization of cytochrome P-450scc from bovine adrenocortical mitochondria.

    abstract::Cytochrome P-450scc (P-450scc), a cholesterol side-chain cleavage enzyme from bovine adrenocortical mitochondria, has been crystallized for the first time. Upon removal of glycerol from the solution of the native enzyme complexed with pyridoxal 5'-phosphate (PLP) by microdialysis against distilled water, reddish and p...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(88)81350-4

    authors: Iwamoto Y,Tsubaki M,Hiwatashi A,Ichikawa Y

    更新日期:1988-06-06 00:00:00

  • Auxin-induced reactive oxygen species production requires the activation of phosphatidylinositol 3-kinase.

    abstract::We recently reported that production of reactive oxygen species (ROS) is essential for auxin-induced gravitropic signaling. Here, we investigated the role of phosphatidylinositol 3-kinase and its product, PtdIns(3)P, in auxin-mediated ROS production and the root gravitropic response. Pretreatment with LY294002, an inh...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2005.01.018

    authors: Joo JH,Yoo HJ,Hwang I,Lee JS,Nam KH,Bae YS

    更新日期:2005-02-14 00:00:00

  • P1,P3-bis(5'-adenosyl)triphosphate (Ap3A) as a substrate and a product of mammalian tryptophanyl-tRNA synthetase.

    abstract::Bovine tryptophanyl-tRNA synthetase (TrpRS, E.C.6.1.1.2) is unable to catalyze in vitro formation of Ap4A in contrast to some other aminoacyl-tRNA synthetases. However, in the presence of L-tryptophan, ATP-Mg2+ and ADP the enzyme catalyzes the Ap3A synthesis via adenylate intermediate. Ap3A (not Ap4A) may serve as a s...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(94)00764-0

    authors: Merkulova T,Kovaleva G,Kisselev L

    更新日期:1994-08-22 00:00:00

  • The transcriptional activator GaaR of Aspergillus niger is required for release and utilization of d-galacturonic acid from pectin.

    abstract::We identified the d-galacturonic acid (GA)-responsive transcriptional activator GaaR of the saprotrophic fungus, Aspergillus niger, which was found to be essential for growth on GA and polygalacturonic acid (PGA). Growth of the ΔgaaR strain was reduced on complex pectins. Genome-wide expression analysis showed that Ga...

    journal_title:FEBS letters

    pub_type: 信件

    doi:10.1002/1873-3468.12211

    authors: Alazi E,Niu J,Kowalczyk JE,Peng M,Aguilar Pontes MV,van Kan JA,Visser J,de Vries RP,Ram AF

    更新日期:2016-06-01 00:00:00

  • Insulin-like growth factor I binding and receptor kinase in red and white muscle.

    abstract::IGF-I receptors were partially purified from red and white skeletal muscle by lectin-affinity chromatography and the resultant fraction was depleted of insulin receptors by insulin affinity chromatography. Equilibrium binding of 125I-IGF-I to receptor preparations from red and white muscle yielded identical Scatchard ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(88)80093-0

    authors: Zorzano A,James DE,Ruderman NB,Pilch PF

    更新日期:1988-07-18 00:00:00

  • Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair.

    abstract::Spectral variants of the green fluorescent protein (GFP) have been extensively used as reporters to image molecular interactions in living cells by fluorescence resonance energy transfer (FRET). However, those GFP variants which are the most efficient donor acceptor pairs for FRET measurements show a high degree of sp...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(02)03508-1

    authors: Zimmermann T,Rietdorf J,Girod A,Georget V,Pepperkok R

    更新日期:2002-11-06 00:00:00

  • New genotypes of TT virus (TTV) and a genotyping assay based on restriction fragment length polymorphism.

    abstract::A phylogenetic analysis, using the open reading frame I sequence of 93 TT viruses (TTV) obtained from various geographical areas, indicated that the virus could be classified into six different genotypes including three hitherto unreported genotypes. The high reliability of the six clusters was confirmed by bootstrap ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(98)01231-9

    authors: Tanaka Y,Mizokami M,Orito E,Ohno T,Nakano T,Kato T,Kato H,Mukaide M,Park YM,Kim BS,Ueda R

    更新日期:1998-10-23 00:00:00

  • Comparing the temperature dependence of FMN to heme electron transfer in full length and truncated inducible nitric oxide synthase proteins.

    abstract::The FMN-heme interdomain (intraprotein) electron transfer (IET) kinetics in full length and oxygenase/FMN (oxyFMN) construct of human iNOS were determined by laser flash photolysis over the temperature range from 283 to 304K. An appreciable increase in the rate constant value was observed with an increase in the tempe...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2011.12.009

    authors: Li W,Chen L,Fan W,Feng C

    更新日期:2012-01-20 00:00:00

  • A cytoplasmic domain is required for the functional interaction of SRI and HtrI in archaeal signal transduction.

    abstract::Phototaxis in the archaeon Halobacterium salinarium is mediated by a stable complex of the photoreceptor sensory rhodopsin I and its transducer HtrI, which relays the light stimulus to the signalling pathway. Removal of the cytoplasmic signalling domain of HtrI eliminated the SRI-specific motor response to light stimu...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(94)01068-4

    authors: Krah M,Marwan W,Oesterhelt D

    更新日期:1994-10-24 00:00:00

  • The orientation of the antibiotic peptide maculatin 1.1 in DMPG and DMPC lipid bilayers. Support for a pore-forming mechanism.

    abstract::Maculatin 1.1 is an antimicrobial peptide isolated from the Australian tree frog Litoria genimaculata that adopts an amphipathic, alpha-helical structure in solution. Its orientation and conformation when incorporated to pre-formed DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) and DMPC (1,2-dimyristoyl-sn-glycer...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(01)03313-0

    authors: Chia CS,Torres J,Cooper MA,Arkin IT,Bowie JH

    更新日期:2002-02-13 00:00:00

  • N-3 PUFAs modulate global gene expression profile in cultured rat cardiomyocytes. Implications in cardiac hypertrophy and heart failure.

    abstract::In cardiac cells the effects of n-3 PUFAs on the whole genome are still unknown despite their recognized cardioprotective effects and ability to modulate gene expression. We have evaluated the effects of n-3 PUFAs supplementation on the global gene expression profile in cultured neonatal rat cardiomyocytes, detecting ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2007.01.070

    authors: Bordoni A,Astolfi A,Morandi L,Pession A,Danesi F,Di Nunzio M,Franzoni M,Biagi P,Pession A

    更新日期:2007-03-06 00:00:00

  • Probing DNA triple helix structure by chemical ligation.

    abstract::A series of oligomeric double and triple helical DNAs with irregular sequences of homopurine and homopyrimidine strands were prepared. DNA triplexes were identified by CD spectroscopy and thermal denaturation profiles (biphasic helix-coil transition). Condensation of oligonucleotides on single and double-stranded DNA ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80692-v

    authors: Dolinnaya NG,Pyatrauskene OV,Shabarova ZA

    更新日期:1991-06-24 00:00:00