sodium dependent organic anion transporters


Summary: A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is driven either directly or indirectly by a gradient of sodium ions.

Top Publications

  1. Wong M, Oelkers P, Dawson P. Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. J Biol Chem. 1995;270:27228-34 pubmed
    ..This dysfunctional mutation represents the first known molecular defect in a human sodium-dependent bile acid transporter. ..
  2. Wong M, Rao P, Pettenati M, Dawson P. Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33. Genomics. 1996;33:538-40 pubmed
  3. Torchia E, Cheema S, Agellon L. Coordinate regulation of bile acid biosynthetic and recovery pathways. Biochem Biophys Res Commun. 1996;225:128-33 pubmed
    ..These results suggest that in mice the bile acid recovery and biosynthetic pathways are coordinately regulated, and these pathways may be responsive to the size of the bile acid pool in the enterohepatic circulation. ..
  4. Oelkers P, Kirby L, Heubi J, Dawson P. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest. 1997;99:1880-7 pubmed
    ..These findings establish that SLC10A2 mutations can cause PBAM and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids. ..
  5. Weinman S, Carruth M, Dawson P. Bile acid uptake via the human apical sodium-bile acid cotransporter is electrogenic. J Biol Chem. 1998;273:34691-5 pubmed
    ..These results suggest that membrane potential may regulate bile acid transport rates under physiological and pathophysiological conditions. ..
  6. Makishima M, Okamoto A, Repa J, Tu H, Learned R, Luk A, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284:1362-5 pubmed
    ..These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport. ..
  7. Wang W, Xue S, Ingles S, Chen Q, Diep A, Frankl H, et al. An association between genetic polymorphisms in the ileal sodium-dependent bile acid transporter gene and the risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 2001;10:931-6 pubmed
  8. Love M, Craddock A, Angelin B, Brunzell J, Duane W, Dawson P. Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2001;21:2039-45 pubmed
    ..These findings indicate that the decreased intestinal bile acid absorption in FHTG patients is not commonly associated with inherited defects in SLC10A2. ..
  9. Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange E. Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers. J Lipid Res. 2006;47:42-50 pubmed
    ..In conclusion, in normal weight female gallstone carriers, the decreased expression of ileal bile acid transporters may form a molecular basis for gallstone formation. ..

More Information

Publications103 found, 100 shown here

  1. Montagnani M, Abrahamsson A, Gälman C, Eggertsen G, Marschall H, Ravaioli E, et al. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption. World J Gastroenterol. 2006;12:7710-4 pubmed
    ..In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM. ..
  2. Renner O, Harsch S, Strohmeyer A, Schimmel S, Stange E. Reduced ileal expression of OSTalpha-OSTbeta in non-obese gallstone disease. J Lipid Res. 2008;49:2045-54 pubmed publisher
  3. Holzer A, Harsch S, Renner O, Strohmeyer A, Schimmel S, Wehkamp J, et al. Diminished expression of apical sodium-dependent bile acid transporter in gallstone disease is independent of ileal inflammation. Digestion. 2008;78:52-9 pubmed publisher
    ..The mechanisms of transcriptional repression of ASBT in both diseases are apparently different. ..
  4. Renner O, Harsch S, Schaeffeler E, Schwab M, Klass D, Kratzer W, et al. Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2): novel haplotype block including six newly identified variants linked to reduced expression. Hum Genet. 2009;125:381-91 pubmed publisher
    ..0157). In future studies a single tag SNP selected of this haplotype block will provide reliable genetic testing to investigate systemically the influence of the SLC10A2 haplotype for disease susceptibility and/or drug response. ..
  5. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier P. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991;88:10629-33 pubmed
    ..Northern blot analysis with the cloned probe revealed crossreactivity with mRNA species from rat kidney and intestine as well as from liver tissues of mouse, guinea pig, rabbit, and man. ..
  6. Parks D, Blanchard S, Bledsoe R, Chandra G, Consler T, Kliewer S, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284:1365-8 pubmed
    ..These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis. ..
  7. Montagnani M, Love M, Rossel P, Dawson P, Qvist P. Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol. 2001;36:1077-80 pubmed
  8. Xia X, Roundtree M, Merikhi A, Lu X, Shentu S, Lesage G. Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes. J Biol Chem. 2004;279:44931-7 pubmed
    ..These studies are the first report of regulation of a bile acid transporter expression by the ubiquitin-proteasome pathway. ..
  9. McRae M, Lowe C, Tian X, Bourdet D, Ho R, Leake B, et al. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther. 2006;318:1068-75 pubmed
    ..Nevirapine (75 microM) had no effect on bile acid transport in any model system. In conclusion, ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibited both the hepatic uptake and biliary excretion of taurocholate. ..
  10. Lutsenko E, Carcamo J, Golde D. A human sodium-dependent vitamin C transporter 2 isoform acts as a dominant-negative inhibitor of ascorbic acid transport. Mol Cell Biol. 2004;24:3150-6 pubmed
    ..These findings suggest a mechanism of AA uptake regulation whereby an alternative SVCT2 gene product inhibits transport through the two known AA transporters. ..
  11. Arab J, Ramirez C, Muñoz P, Pizarro M, Solis N, Riquelme A, et al. Effects of Japanese herbal medicine Inchin-ko-to on endotoxin-induced cholestasis in the rat. Ann Hepatol. 2009;8:228-33 pubmed
    ..Our data show that oral supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bile salt-independent flow. ..
  12. Hagenbuch B, Meier P. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. J Clin Invest. 1994;93:1326-31 pubmed
    ..Southern blot analysis of genomic DNA from a panel of human/hamster somatic cell hybrids mapped the human NTCP gene to chromosome 14. ..
  13. Li D, Zimmerman T, Thevananther S, Lee H, Kurie J, Karpen S. Interleukin-1 beta-mediated suppression of RXR:RAR transactivation of the Ntcp promoter is JNK-dependent. J Biol Chem. 2002;277:31416-22 pubmed
  14. Takanaga H, Mackenzie B, Hediger M. Sodium-dependent ascorbic acid transporter family SLC23. Pflugers Arch. 2004;447:677-82 pubmed
    ..An SVCT2-knockout mouse reveals an obligatory requirement for SVCT2, but many of the specific roles of this transporter remain unclear. ..
  15. Xia X, Francis H, Glaser S, Alpini G, Lesage G. Bile acid interactions with cholangiocytes. World J Gastroenterol. 2006;12:3553-63 pubmed
    ..Based upon these concepts and observations, the cholangiocyte has been proposed to be the principle target cell for bile acids in the liver. ..
  16. Renner O, Harsch S, Schaeffeler E, Winter S, Schwab M, Krawczyk M, et al. A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PLoS ONE. 2009;4:e7321 pubmed publisher
    ..The minor allele of rs9514089 is related to differences in plasma cholesterol levels among the subjects. ..
  17. Lucke C, Zhang F, Hamilton J, Sacchettini J, Rüterjans H. Solution structure of ileal lipid binding protein in complex with glycocholate. Eur J Biochem. 2000;267:2929-38 pubmed
    ..Furthermore, this binding mode explains how ILBP can transport unconjugated and conjugated bile acids. ..
  18. Saeki T, Takahashi N, Kanamoto R, Iwami K. Characterization of cloned mouse Na+/taurocholate cotransporting polypeptide by transient expression in COS-7 cells. Biosci Biotechnol Biochem. 2002;66:1116-8 pubmed
    ..This Km value is comparable to that for rat NTCP and higher than that for human NTCP. Substrate specificity was evaluated by measuring inhibitory effects of unlabeled bile acids on [3H]taurocholic acid transport. ..
  19. Chen F, Ma L, Dawson P, Sinal C, Sehayek E, Gonzalez F, et al. Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter. J Biol Chem. 2003;278:19909-16 pubmed
    ..In summary cell line- and species-specific negative feedback regulation of ASBT by bile acids is mediated by farnesoid X receptor via small heterodimer partner-dependent repression of LRH-1 activation of the ASBT promoter. ..
  20. Timpson N, Forouhi N, Brion M, Harbord R, Cook D, Johnson P, et al. Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with >15,000 participants. Am J Clin Nutr. 2010;92:375-82 pubmed publisher
    ..This finding has implications more generally for the epidemiologic investigation of relations between circulating L-ascorbic acid and health outcomes. ..
  21. Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton C, Hediger M. Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem Biophys Res Commun. 2000;267:488-94 pubmed
    ..The molecular identification of the human l-ascorbic acid transporters now provides the tools with which to investigate their roles in vitamin C metabolism in health and disease. ..
  22. Fujita T, Katsukawa H, Yodoya E, Wada M, Shimada A, Okada N, et al. Transport characteristics of N-acetyl-L-aspartate in rat astrocytes: involvement of sodium-coupled high-affinity carboxylate transporter NaC3/NaDC3-mediated transport system. J Neurochem. 2005;93:706-14 pubmed
    ..This transporter is likely to be an essential prerequisite for the metabolic role of N-acetyl-L-aspartate in the process of myelination. ..
  23. Varma S, Campbell C, Kuo S. Functional role of conserved transmembrane segment 1 residues in human sodium-dependent vitamin C transporters. Biochemistry. 2008;47:2952-60 pubmed publisher
  24. Fan X, Monnier V. Vitamin C-mediated Maillard reaction in the lens probed in a transgenic-mouse model. Ann N Y Acad Sci. 2008;1126:194-200 pubmed publisher
    ..Treatment of the mice with nucleophilic inhibitors can slow down the process, opening new avenues for the pharmacological prevention of senile cataractogenesis. ..
  25. Pajor A, Sun N. Molecular cloning, chromosomal organization, and functional characterization of a sodium-dicarboxylate cotransporter from mouse kidney. Am J Physiol Renal Physiol. 2000;279:F482-90 pubmed
    ..However, its function more closely resembles the rabbit and human orthologs rather than the rat NaDC-1, with which it shares higher sequence similarity...
  26. Gälman C, Ostlund Lindqvist A, Björquist A, Schreyer S, Svensson L, Angelin B, et al. Pharmacological interference with intestinal bile acid transport reduces plasma cholesterol in LDL receptor/apoE deficiency. FASEB J. 2003;17:265-7 pubmed
    ..These effects could not be attributed to induction of other known hepatic lipoprotein receptors and indicate the presence of new points of targeting in lipid-lowering therapy. ..
  27. Liu Y, Binz J, Numerick M, Dennis S, Luo G, Desai B, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest. 2003;112:1678-87 pubmed
    ..The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease...
  28. Corti A, Casini A, Pompella A. Cellular pathways for transport and efflux of ascorbate and dehydroascorbate. Arch Biochem Biophys. 2010;500:107-15 pubmed publisher
    ..Altogether, available data suggest that cellular efflux of ascorbic acid - besides its uptake - should be taken into account when evaluating the cellular homeostasis and functions of this important vitamin. ..
  29. Pajor A. Sodium-coupled transporters for Krebs cycle intermediates. Annu Rev Physiol. 1999;61:663-82 pubmed
    ..The current model of secondary structure in NaDC-1 contains 11 transmembrane domains and an extracellular N-glycosylated carboxy terminus. ..
  30. Torchia E, Stolz A, Agellon L. Differential modulation of cellular death and survival pathways by conjugated bile acids. BMC Biochem. 2001;2:11 pubmed
    ..Additionally, activation of a signaling pathway involving PI3K appears to be the dominant mechanism responsible for the tolerance of McNtcp.24 cells to taurine-conjugated bile acids. ..
  31. He Y, Chen X, Yu Z. [The change of human Na+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with pathogenesis of nephrolithiasis]. Zhonghua Yi Xue Za Zhi. 2001;81:1066-9 pubmed
    ..The upregulation of hNaDC1 mRNA and protein abundance in the kidney may be an important cause of hypocitraturia, which might be related with the occurrence and recurrence of nephrolithiasis. ..
  32. Labonté E, Li Q, Kay C, Agellon L. The relative ligand binding preference of the murine ileal lipid binding protein. Protein Expr Purif. 2003;28:25-33 pubmed
    ..Among the bile acids, mILBP showed the greatest preference for conjugated species that contained a doubly hydroxylated steroid moiety. The results demonstrate that mILBP exhibits a preference for certain species of bile and fatty acids. ..
  33. McNulty A, Vail T, Kraus V. Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochim Biophys Acta. 2005;1712:212-21 pubmed
    ..Thus, we provide the first evidence that SVCT2 mediates the secondary active and concentrative transport of ascorbic acid in human chondrocytes. ..
  34. Bai X, Chen X, Sun A, Feng Z, Hou K, Fu B. Membrane topology structure of human high-affinity, sodium-dependent dicarboxylate transporter. FASEB J. 2007;21:2409-17 pubmed
    ..Our results support the topography of 11 transmembrane domains with an extracellular C terminus and an intracellular N terminus of NaDC3, and for the first time provide experimental evidence for a novel topological model for NaDC3. ..
  35. Bornstein S, Yoshida Hiroi M, Sotiriou S, Levine M, Hartwig H, Nussbaum R, et al. Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2). FASEB J. 2003;17:1928-30 pubmed
    ..The data, however, establish a crucial role for ascorbic acid in adrenal chromaffin cell function. ..
  36. Alrefai W, Saksena S, Tyagi S, Gill R, Ramaswamy K, Dudeja P. Taurodeoxycholate modulates apical Cl-/OH- exchange activity in Caco2 cells. Dig Dis Sci. 2007;52:1270-8 pubmed
    ..In conclusion, our studies provide direct evidence for inhibition of human intestinal apical Cl(-)/OH(-) exchange activity by bile acids via Ca(2+)-, PI3 kinase-, and PKC beta I-dependent pathways in Caco2 cells. ..
  37. Lee J, Azzaroli F, Wang L, Soroka C, Gigliozzi A, Setchell K, et al. Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. Gastroenterology. 2001;121:1473-84 pubmed
    ..These responses may facilitate extrahepatic pathways for bile salt excretion during cholestasis. ..
  38. Clark A, Rohrbaugh A, Otterness I, Kraus V. The effects of ascorbic acid on cartilage metabolism in guinea pig articular cartilage explants. Matrix Biol. 2002;21:175-84 pubmed
    ..Therefore, this transporter may be the primary mechanism by which the L-forms of ascorbic acid enter the chondrocyte to control matrix gene activity...
  39. Bulgakova N, Trunova S, Omel ianchuk L. [Identification of Indy(p115) mutation in the Na+-dicarboxylate transporter gene in Drosophila melanogaster]. Genetika. 2002;38:41-5 pubmed
    ..The expression pattern of this gene seems also to account for the tissue- and stage-specific activity of the 5'-regulatory region in the Indy gene. ..
  40. Bolder U, Schmidt A, Landmann L, Kidder V, Tange S, Jauch K. Heat stress prevents impairment of bile acid transport in endotoxemic rats by a posttranscriptional mechanism. Gastroenterology. 2002;122:963-73 pubmed
    ..Because heat stress ameliorates other sequelae of endotoxemia, studies were performed to determine whether heat stress would correct deficient bile acid transport caused by endotoxin...
  41. Elferink M, Olinga P, Draaisma A, Merema M, Faber K, Slooff M, et al. LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process. Am J Physiol Gastrointest Liver Physiol. 2004;287:G1008-16 pubmed
    ..In conclusion, we show that posttranscriptional mechanisms play a more prominent role in LPS-induced regulation of human MRP2 and BSEP compared with the rat transporter proteins...
  42. Chan J, Donalson L, Kushwaha R, Ferdinandusse S, VandeBerg J, Vandeberg J. Differential expression of hepatic genes involved in cholesterol homeostasis in high- and low-responding strains of laboratory opossums. Metabolism. 2008;57:718-24 pubmed publisher
    ..Low levels of CYP27A1, ABCG5, and ABCG8 expression in the liver may contribute to hypercholesterolemia in high-responding opossums...
  43. Hakansson P, Andersson I, Nystrom S, Lofgren L, Amrot L, Li H. Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice. Scand J Gastroenterol. 2002;37:1089-96 pubmed
    ..The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice. ..
  44. Kip N, Lazaridis K, Masyuk A, Splinter P, Huebert R, Larusso N. Differential expression of cholangiocyte and ileal bile acid transporters following bile acid supplementation and depletion. World J Gastroenterol. 2004;10:1440-6 pubmed
    ..Thus, while transcriptional regulatory mechanisms in response to alterations in bile acid pool size are operative in both cholangiocytes and ileocytes, each cell type responds differently to bile acid supplementation and depletion. ..
  45. Tsuboi K, Tazuma S, Nishioka T, Chayama K. Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage. J Gastroenterol. 2004;39:955-60 pubmed
    ..Thus, the modulation of lecithin secretion into bile may be another important target for the treatment of biliary disorders. ..
  46. Zollner G, Wagner M, Fickert P, Geier A, Fuchsbichler A, Silbert D, et al. Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver. Am J Physiol Gastrointest Liver Physiol. 2005;289:G798-805 pubmed
  47. Alrefai W, Sarwar Z, Tyagi S, Saksena S, Dudeja P, Gill R. Cholesterol modulates human intestinal sodium-dependent bile acid transporter. Am J Physiol Gastrointest Liver Physiol. 2005;288:G978-85 pubmed
    ..These data provide novel evidence for the direct regulation of human ASBT function by cholesterol and suggest that this phenomenon may play a central role in cholesterol homeostasis. ..
  48. Banerjee A, Hussainzada N, Khandelwal A, Swaan P. Electrostatic and potential cation-pi forces may guide the interaction of extracellular loop III with Na+ and bile acids for human apical Na+-dependent bile acid transporter. Biochem J. 2008;410:391-400 pubmed
    ..We conclude that EL3 amino acids are essential for hASBT activity, probably as primary substrate interaction points using long-range electrostatic attractive forces. ..
  49. Crossman M, Hauft S, Gordon J. The mouse ileal lipid-binding protein gene: a model for studying axial patterning during gut morphogenesis. J Cell Biol. 1994;126:1547-64 pubmed
  50. Liang W, Johnson D, Jarvis S. Vitamin C transport systems of mammalian cells. Mol Membr Biol. 2001;18:87-95 pubmed
    ..The two isoforms also differ in their tissue distribution: SVCT1 is present in epithelial tissues, whereas SVCT2 is present in most tissues with the exception of lung and skeletal muscle. ..
  51. Fei Y, Inoue K, Ganapathy V. Structural and functional characteristics of two sodium-coupled dicarboxylate transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and their relevance to life span. J Biol Chem. 2003;278:6136-44 pubmed
    ..elegans may lead to decreased availability of dicarboxylates for cellular production of metabolic energy, thus creating a biological state similar to that of caloric restriction, and consequently leading to life span extension. ..
  52. Savini I, Catani M, Duranti G, Ceci R, Sabatini S, Avigliano L. Vitamin C homeostasis in skeletal muscle cells. Free Radic Biol Med. 2005;38:898-907 pubmed
    ..From our data, SVCT2 and NADPH-thioredoxin-dependent DHA reduction appears to belong to an inducible system activated in response to oxidative stress. ..
  53. Zou X, Wang D, Qiu G, Ji C, Jin F, Wu M, et al. Molecular cloning and characterization of a novel human C4orf13 gene, tentatively a member of the sodium bile acid cotransporter family. Biochem Genet. 2005;43:165-73 pubmed
  54. Saeki T, Munetaka Y, Ueda K, Iwami K, Kanamoto R. Effects of Ala substitution for conserved Cys residues in mouse ileal and hepatic Na+-dependent bile acid transporters. Biosci Biotechnol Biochem. 2007;71:1865-72 pubmed
    ..The K(m) values for TCA uptake by these mutants were comparable, suggesting that these residues are not involved in the interaction with TCA. ..
  55. Chen B, Kuo K, Chen K, Liu C, Tsai L, Hsu H, et al. Retinoid X receptor alpha participation in dexamethasone-induced rat bile acid coenzyme A-amino acid N-acyltransferase expression in septic liver. Shock. 2009;32:164-71 pubmed publisher
    ..In an experiment to confirm our findings, RXR[alpha] siRNA was found to significantly block Dex-induced increases in expression of rBAT in hepatocytes taken from septic rats (P < 0.01)...
  56. Qiao H, Li L, Qu Z, May J. Cobalt-induced oxidant stress in cultured endothelial cells: prevention by ascorbate in relation to HIF-1alpha. Biofactors. 2009;35:306-13 pubmed publisher
  57. Zheng X, Diao L, Ekins S, Polli J. Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies. Biochem Pharmacol. 2010;80:1087-92 pubmed publisher
    ..Drug cytotoxicity varied in different cell lines, which could increase false positives for pharmacophore development. ..
  58. Geier A, Dietrich C, Lammert F, Orth T, Mayet W, Matern S, et al. Regulation of organic anion transporters in a new rat model of acute and chronic cholangitis resembling human primary sclerosing cholangitis. J Hepatol. 2002;36:718-24 pubmed
    ..This might represent the first injury to hepatocytes in chronic cholangitis as an extension of liver injury from the level of cholangiocytes to hepatocytes in PSC. ..
  59. Huff M, Telford D, Edwards J, Burnett J, Barrett P, Rapp S, et al. Inhibition of the apical sodium-dependent bile acid transporter reduces LDL cholesterol and apoB by enhanced plasma clearance of LDL apoB. Arterioscler Thromb Vasc Biol. 2002;22:1884-91 pubmed
    ..A low dose of the ASBT inhibitor, SC-435, significantly reduces plasma LDL cholesterol through enhanced LDL receptor-mediated LDL apoB clearance, secondary to increased expression of cholesterol 7alpha-hydroxylase. ..
  60. Geier A, Dietrich C, Voigt S, Kim S, Gerloff T, Kullak Ublick G, et al. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Hepatology. 2003;38:345-54 pubmed
    ..In contrast to in vitro studies, HNF1 and RXR/RAR-independent mechanisms appear to be more important in regulation of Mrp2 and Ntcp gene expression in endotoxemia...
  61. Wu X, Itoh N, Taniguchi T, Hirano J, Nakanishi T, Tanaka K. Stimulation of differentiation in sodium-dependent vitamin C transporter 2 overexpressing MC3T3-E1 osteoblasts. Biochem Biophys Res Commun. 2004;317:1159-64 pubmed
    ..These findings indicate that SVCT2 stimulates osteoblast differentiation and mineralization. ..
  62. West K, McGrane M, Odom D, Keller B, Fernandez M. SC-435, an ileal apical sodium-codependent bile acid transporter inhibitor alters mRNA levels and enzyme activities of selected genes involved in hepatic cholesterol and lipoprotein metabolism in guinea pigs. J Nutr Biochem. 2005;16:722-8 pubmed
    ..These results suggest that both SC-435 monotherapy and combination therapy lower LDL cholesterol concentrations by altering both hepatic cholesterol homeostasis and the intravascular processing of lipoproteins in guinea pigs. ..
  63. Ray A, Banerjee A, Chang C, Khantwal C, Swaan P. Design of novel synthetic MTS conjugates of bile acids for site-directed sulfhydryl labeling of cysteine residues in bile acid binding and transporting proteins. Bioorg Med Chem Lett. 2006;16:1473-6 pubmed
    ..8+/-0.3, 24.03+/-1.22, 46.49+/-5.01 pmol mg protein min(-1), respectively). These compounds prove to be effective tools in probing the structural and functional effects of cysteine residues in bile acid binding and transporting proteins. ..
  64. Kubitz R, Helmer A, Haussinger D. Biliary transport systems: short-term regulation. Methods Enzymol. 2005;400:542-57 pubmed
    ..Different techniques have been employed in studies on transporter retrieval and insertion, which are discussed in this chapter. ..
  65. Neimark E, Chen F, Li X, Magid M, Alasio T, Frankenberg T, et al. c-Fos is a critical mediator of inflammatory-mediated repression of the apical sodium-dependent bile acid transporter. Gastroenterology. 2006;131:554-67 pubmed
    ..Indomethacin-induced ileal injury was greater in the c-fos-null mice compared with the wild-type littermates. Human, rat, and mouse ASBT is inhibited by inflammatory cytokines via direct interactions of c-fos with the ASBT promoter. ..
  66. van der Deure W, Peeters R, Visser T. Genetic variation in thyroid hormone transporters. Best Pract Res Clin Endocrinol Metab. 2007;21:339-50 pubmed
    ..However, with the characterization of specific thyroid hormone transporters, a new field of research is emerging. ..
  67. Perez M, Castaño B, Gonzalez Buitrago J, Marin J. Multiple protective effects of melatonin against maternal cholestasis-induced oxidative stress and apoptosis in the rat fetal liver-placenta-maternal liver trio. J Pineal Res. 2007;43:130-9 pubmed
  68. Gonzalez P, Acharya C, MacKerell A, Polli J. Inhibition requirements of the human apical sodium-dependent bile acid transporter (hASBT) using aminopiperidine conjugates of glutamyl-bile acids. Pharm Res. 2009;26:1665-78 pubmed publisher
    ..Aminopiperidine conjugates of glu-BAs were potent hASBT inhibitors. A predictive and robust CSP-SAR model was developed. ..
  69. Pajor A. Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney. Am J Physiol. 1996;270:F642-8 pubmed
  70. Hallen S, Mareninova O, Branden M, Sachs G. Organization of the membrane domain of the human liver sodium/bile acid cotransporter. Biochemistry. 2002;41:7253-66 pubmed
    ..These findings support a topography with nine membrane-spanning or membrane-associated segments. ..
  71. Wolters H, Elzinga B, Baller J, Boverhof R, Schwarz M, Stieger B, et al. Effects of bile salt flux variations on the expression of hepatic bile salt transporters in vivo in mice. J Hepatol. 2002;37:556-63 pubmed
    ..We investigated the physiological relevance of this regulation by evaluating transporter expression in mice experiencing different transhepatic bile salt fluxes...
  72. Tollefson M, Kolodziej S, Fletcher T, Vernier W, Beaudry J, Keller B, et al. A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines. Bioorg Med Chem Lett. 2003;13:3727-30 pubmed
    ..Several 1,2-benzothiazepines exhibited low nanomolar in vitro activity. The synthesis and initial in vitro potency data is presented for this novel class of compounds. ..
  73. Geuken E, Visser D, Kuipers F, Blokzijl H, Leuvenink H, de Jong K, et al. Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation. J Hepatol. 2004;41:1017-25 pubmed
    ..This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation. ..
  74. Hulzebos C, Voshol P, Wolters H, Kruit J, Ottenhof R, Groen A, et al. Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice. Liver Int. 2005;25:604-12 pubmed
    ..Bile duct proliferation in Mdr2(-/-) mice enhances cholehepatic shunting of bile salts, which is associated with a disproportionally high bile flow but does not affect bile salt synthesis. ..
  75. Jin S, Mun G, Lee J, Oh C, Kim J, Chung Y, et al. Immunohistochemical study on the distribution of sodium-dependent vitamin C transporters in the respiratory system of adult rat. Microsc Res Tech. 2005;68:360-7 pubmed
  76. Liu Y, Havinga R, van der Leij F, Boverhof R, Sauer P, Kuipers F, et al. Dexamethasone exposure of neonatal rats modulates biliary lipid secretion and hepatic expression of genes controlling bile acid metabolism in adulthood without interfering with primary bile acid kinetics. Pediatr Res. 2008;63:375-81 pubmed publisher
    ..Therefore, neonatal DEX administration causes altered gene expressions later in life that are not translated into quantitative changes in bile acid kinetics. ..
  77. Kidd M, Modlin I, Gustafsson B, Drozdov I, Hauso O, Pfragner R. Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol. 2008;295:G260-72 pubmed publisher
    ..Luminal EC cell regulation is likely to be as important as G cell regulation in gastric acid secretion; development of agents to target EC cell function is therefore a critical therapeutic goal...
  78. Zheng X, Ekins S, Raufman J, Polli J. Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter. Mol Pharm. 2009;6:1591-603 pubmed publisher
    ..In summary, using a combined in vitro and computational approach, we found that many FDA-approved drugs from diverse classes, such as the dihydropyridine calcium channel blockers and HMG CoA-reductase inhibitors, are ASBT inhibitors. ..
  79. Schonhoff C, Yamazaki A, Hohenester S, Webster C, Bouscarel B, Anwer M. PKC{epsilon}-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1259-67 pubmed publisher
    ..Taken together, these results suggest that TLC-induced inhibition of PKB, but not of TC uptake, is mediated via nPKCepsilon. Activation of nPKCepsilon and inhibition of TC uptake by TLC are not mediated via the PI3K/PKB pathway. ..
  80. Erichsen H, Eck P, Levine M, Chanock S. Characterization of the genomic structure of the human vitamin C transporter SVCT1 (SLC23A2). J Nutr. 2001;131:2623-7 pubmed
    ..Our findings will serve as the foundation for investigation of the regulation and expression of the tissue-specific sodium-dependent vitamin C transporter, SLC23A2. ..
  81. Gamba G. Alternative splicing and diversity of renal transporters. Am J Physiol Renal Physiol. 2001;281:F781-94 pubmed
    ..Different regulation among isoforms is an interesting possibility. Thus the diversity of several renal transporters is enhanced by alternative splicing mechanisms...
  82. Yao X, Pajor A. Arginine-349 and aspartate-373 of the Na(+)/dicarboxylate cotransporter are conformationally sensitive residues. Biochemistry. 2002;41:1083-90 pubmed
    ..We conclude that the accessibility of Arg-349 and Asp-373 is likely to change with the conformational states of the transport cycle. ..
  83. Tirona R, Leake B, Wolkoff A, Kim R. Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003;304:223-8 pubmed
    ..This is the first demonstration of an uptake transporter such as OATP-C, in modulating PXR function, and sheds important new insight into our understanding of the molecular determinants of PXR-mediated inductive processes. ..
  84. Ho R, Leake B, Roberts R, Lee W, Kim R. Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J Biol Chem. 2004;279:7213-22 pubmed
    ..Accordingly, our study indicates functionally important polymorphisms in NTCP exist and that the likelihood of being carriers of such polymorphisms is dependent on ethnicity. ..
  85. Monteiro I, David E, Ferraris R. Ontogenetic development of rat intestinal bile acid transport requires thyroxine but not corticosterone. Pediatr Res. 2004;55:611-21 pubmed
    ..Hence, endogenous thyroxine but not corticosterone regulates the developmentally timed appearance of ASBT. ..
  86. Chang P, Hung D, Siebert G, Bridle K, Roberts M. Therapeutic effects and possible mechanisms of a snake venom preparation in the fibrotic rat liver. Dig Dis Sci. 2005;50:745-52 pubmed
  87. Bijvelds M, Jorna H, Verkade H, Bot A, Hofmann F, Agellon L, et al. Activation of CFTR by ASBT-mediated bile salt absorption. Am J Physiol Gastrointest Liver Physiol. 2005;289:G870-9 pubmed
    ..We conclude that active BS absorption in the ileum triggers CFTR activation and, consequently, local salt and water secretion, which may serve to prevent intestinal obstruction in the postprandial state. ..
  88. Weihrauch D, Kanchanapoo J, Ao M, Prasad R, Piyachaturawat P, Rao M. Weanling, but not adult, rabbit colon absorbs bile acids: flux is linked to expression of putative bile acid transporters. Am J Physiol Gastrointest Liver Physiol. 2006;290:G439-50 pubmed
  89. Vicens M, Macias R, Briz O, Rodriguez A, El Mir M, Medarde M, et al. Inhibition of the intestinal absorption of bile acids using cationic derivatives: mechanism and repercussions. Biochem Pharmacol. 2007;73:394-404 pubmed
    ..In sum, our results suggest that these compounds, in particular BAPA-3, are potentially useful tools for inhibiting the intestinal absorption of bile acids in a non-competitive manner. ..
  90. Geier A, Martin I, Dietrich C, Balasubramaniyan N, Strauch S, Suchy F, et al. Hepatocyte nuclear factor-4alpha is a central transactivator of the mouse Ntcp gene. Am J Physiol Gastrointest Liver Physiol. 2008;295:G226-33 pubmed publisher
    ..Using Hepa 1-6 cells, HNF-4alpha-knockdown resulted in a significant 95% reduction in NTCP mRNA. In conclusion, mouse Ntcp is regulated by HNF-4alpha via a conserved distal cis-element independently of HNF-1alpha. ..
  91. Reidling J, Subramanian V, Dahhan T, Sadat M, Said H. Mechanisms and regulation of vitamin C uptake: studies of the hSVCT systems in human liver epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;295:G1217-27 pubmed publisher
    ..These studies are the first to determine the overall ascorbic acid uptake process and relative expression, regulation, and contribution of the hSVCT systems in human liver epithelial cells. ..
  92. Zarebkohan A, Javan M, Satarian L, Ahmadiani A. Effect of chronic administration of morphine on the gene expression level of sodium-dependent vitamin C transporters in rat hippocampus and lumbar spinal cord. J Mol Neurosci. 2009;38:236-42 pubmed publisher
    ..SVCT1 did not express in control or morphine-treated rats. It seems that reduced expression level of SVCT2 might be involved in the development of morphine side effects such as tolerance and dependency. ..