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Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR 被引量:5
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作者 Wolfgang Wistuba Carsten Gnewuch +2 位作者 Gerhard Liebisch Gerd Schmitz Thomas Langmann 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第31期4230-4235,共6页
To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response... To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response of the FGF19 promoter region. METHODS: The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxy- cholic acid and lithocholic acid for several time points. FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors, RESULTS: LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two poten- tial binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor (RXR) and stimulation with LCA or the potent PXR ligand rifampicin leads to a significant induction of FGF19 promoter activ- ity in intestinal cells. CONCLUSION: LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression. 展开更多
关键词 Pregnane X receptor DETOXIFICATION Fibroblast growth factor 19 lithocholic acid
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Facially amphiphilic polyionene biocidal polymers derived from lithocholic acid 被引量:1
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作者 Mitra S.Ganewatta Md Anisur Rahman +4 位作者 Louis Mercado Tinom Shokfai Alan W.Decho Theresa M.Reineke Chuanbing Tang 《Bioactive Materials》 SCIE 2018年第2期186-193,共8页
Bacterial infections have become a global issue that requires urgent attention,particularly regarding to emergence of multidrug resistant bacteria.We developed quaternary amine-containing antimicrobial poly(bile acid)... Bacterial infections have become a global issue that requires urgent attention,particularly regarding to emergence of multidrug resistant bacteria.We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain.Interestingly,by choosing appropriate monomers,these cationic polymers can form core-shell micelles.These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species.It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities.Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers. 展开更多
关键词 Antimicrobial polymers Bile acid Quaternary ammonium lithocholic acid Polyionene Facial amphiphilicity
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Secondary bile acids and the biliary epithelia: The good and the bad 被引量:1
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作者 Ilaria Lenci Martina Milana +2 位作者 Alessandro Signorello Giuseppe Grassi Leonardo Baiocchi 《World Journal of Gastroenterology》 SCIE CAS 2023年第2期357-366,共10页
The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocy... The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocytes)in bile formation.The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases,such as primary biliary cholangitis or primary sclerosing cholangitis.Bile acids(BAs),produced by the liver,are the most represented organic molecules in bile.The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules.In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary(deriving by bacterial manipulation of primary molecules)ones.This class of BAs is demonstrated to have relevant biological effects,ranging from toxic to therapeutic ones.In this family ursodeoxycholic and lithocholic acid present the most interesting features.The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage.These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders. 展开更多
关键词 CHOLANGIOCYTES Biliary secretion CHOLESTASIS Bile acids Secondary bile acids Ursodeoxycholic acid lithocholic acid
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Oxidative stress, antioxidants and intestinal calcium absorption 被引量:20
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作者 Gabriela Diaz de Barboza Solange Guizzardi +1 位作者 Luciana Moine Nori Tolosa de Talamoni 《World Journal of Gastroenterology》 SCIE CAS 2017年第16期2841-2853,共13页
The disequilibrium between the production of reactive oxygen(ROS) and nitrogen(RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-produ... The disequilibrium between the production of reactive oxygen(ROS) and nitrogen(RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione(GSH) and GSH-dependent enzymes as major components. When the ROS and/or RNS production is exacerbated, oxidative stress occurs and the intestinal Ca2+ absorption is inhibited. GSH depleting drugs such as DLbuthionine-S,R-sulfoximine, menadione and sodium deoxycholate inhibit the Ca2+ transport from lumen to blood by alteration in the protein expression and/or activity of molecules involved in the Ca2+ transcellular and paracellular pathways through mechanisms of oxidative stress, apoptosis and/or autophagy. Quercetin, melatonin, lithocholic and ursodeoxycholic acids block the effect of those drugs in experimental animals by their antioxidant, anti-apoptotic and/or anti-autophagic properties. Therefore, they may become drugs of choice for treatment of deteriorated intestinal Ca2+ absorption under oxidant conditions such as aging, diabetes, gut inflammation and other intestinal disorders. 展开更多
关键词 Transcellular and paracellular Ca2+pathways DL-buthionine-S R-sulfoximine MENADIONE Sodium deoxycholate lithocholic acid Ursodeoxycholic acid MELATONIN
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