The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

SLC10A1  -  solute carrier family 10 (sodium/bile acid...

Homo sapiens

Synonyms: Cell growth-inhibiting gene 29 protein, GIG29, NTCP, Na(+)/bile acid cotransporter, Na(+)/taurocholate transport protein, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of SLC10A1

  • In rat livers cholestasis was induced by PMA (100 nmol) and MRP2 was detected at the basolateral membrane in some areas, colocalizing with Ntcp [1].
  • In patients with biliary atresia, all the genes tested showed higher mean expression levels than adults except for NTCP, but not statistically significant [2].
  • METHODS: Expression of the Na(+)-taurocholate-cotransporting polypeptide (NTCP) was analyzed in six hepatocellular carcinomas and in nonmalignant liver tissue [3].
  • The level of NTCP mRNA in carcinomas amounted to 56% +/- 27% compared with peritumor tissue [3].
  • The recent cloning of a human sodium-dependent bile acid transporter (NTCP) permits analysis of its expression in human liver disease and investigation of potential primary defects in its expression [4].
 

High impact information on SLC10A1

 

Chemical compound and disease context of SLC10A1

 

Biological context of SLC10A1

  • Mutational analysis of the hNTCP promoter identified a functional GR response element, with which GR directly interacts within living cells [8].
  • NTCP and the ileal transporter ASBT (apical sodium-dependent bile acid transporter) are two sodium-dependent transporters critical for the enterohepatic circulation of bile acids [8].
  • Transient transfection demonstrated that SLC10A1 promoter expression was selectively expressed eightfold in FAO and rat hepatocytes, while deletion mutants demonstrated liver-specific expression in a region extending from -5 to +198 bp, which contained putative sites for C/EBP and HNF3 [9].
  • SLC10A1 spans approximately 23 kb distributed over five exons [9].
  • These studies demonstrate that the TATA-less human SLC10A1 promoter exhibits liver-specific activity and its regulatory elements contain binding sites for C/EBP, which contributes specifically to its transcriptional regulation [9].
 

Anatomical context of SLC10A1

  • Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs [10].
  • Na+-taurocholate cotransporting polypeptide (NTCP) is the major bile acid uptake system in human hepatocytes [8].
  • Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp [11].
  • A weak cytostatic effect of BANB-1, BANB-2 and BANB-3 was detected even in CHO cells stably transfected with rat bile acid transporters (Ntcp and Oatp1/1a1) [12].
  • METHODS: Primary rat hepatocytes or transfected HepG2 and Cos cells were treated with retinoids with or without bile acids, and effects on bile acid transport and ntcp and shp gene expression and promoter activity were determined [13].
 

Associations of SLC10A1 with chemical compounds

  • The GR/dexamethasone activation of endogenous hNTCP expression was suppressed by bile acids, in a manner dependent on the bile acid receptor farnesoid X receptor [8].
  • Bile salts are rapidly removed from the circulation by the liver-specific sodium/taurocholate cotransporter (SLC10A1) [9].
  • CONCLUSION: To date, we have shown that this protein has no capacity to transport taurocholate relative to SLC10A1; however, given its ubiquitous tissue distribution, it may play a more active role in transporting other endogenous organic anions [14].
  • [(3)H]Taurocholate transport by recombinant NTCP and Ntcp was inhibited by ritonavir (IC(50) = 2.1 and 6.4 microM in human and rat, respectively), saquinavir (IC(50) = 6.7 and 20 microM, respectively), and efavirenz (IC(50) = 43 and 97 microM, respectively) [15].
  • The well known cholestatic drugs, rifampicin, rifamycin SV, glibenclamide, and cyclosporin A, reduced the basal-to-apical transport and the apical efflux clearance of taurocholate across NTCP- and BSEP-coexpressing cell monolayers [10].
 

Regulatory relationships of SLC10A1

  • In conclusion, the hNTCP promoter is activated by GR in a ligand-dependent manner, similarly to the hASBT promoter [8].
 

Other interactions of SLC10A1

  • SHP is a transcriptional repressor that mediates bile acid-induced repression of the bile salt uptake systems rat Ntcp and human OATP-C [16].
  • Further analysis indicated that the drugs inhibited both NTCP and BSEP [10].
  • NTCP and OATP2 expression was markedly reduced in most HCCs (P < 0.05) [17].
  • Cholesterol 7alpha-hydroxylase (CYP7A1) and Na+/taurocholate-cotransporting polypeptide (NTCP) were upregulated 84- and 8-fold, respectively [18].
  • This was shown by its colocalization with MRP1, human dipeptidylpeptidase IV (DPPIV), and transfected rat Ntcp [1].
 

Analytical, diagnostic and therapeutic context of SLC10A1

References

  1. Protein kinase C-dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells. Kubitz, R., Huth, C., Schmitt, M., Horbach, A., Kullak-Ublick, G., Häussinger, D. Hepatology (2001) [Pubmed]
  2. Developmental expression of canalicular transporter genes in human liver. Chen, H.L., Chen, H.L., Liu, Y.J., Feng, C.H., Wu, C.Y., Shyu, M.K., Yuan, R.H., Chang, M.H. J. Hepatol. (2005) [Pubmed]
  3. Chlorambucil-taurocholate is transported by bile acid carriers expressed in human hepatocellular carcinomas. Kullak-Ublick, G.A., Glasa, J., Böker, C., Oswald, M., Grützner, U., Hagenbuch, B., Stieger, B., Meier, P.J., Beuers, U., Kramer, W., Wess, G., Paumgartner, G. Gastroenterology (1997) [Pubmed]
  4. Hepatic basolateral sodium-dependent-bile acid transporter expression in two unusual cases of hypercholanemia and in extrahepatic biliary atresia. Shneider, B.L., Fox, V.L., Schwarz, K.B., Watson, C.L., Ananthanarayanan, M., Thevananther, S., Christie, D.M., Hardikar, W., Setchell, K.D., Mieli-Vergani, G., Suchy, F.J., Mowat, A.P. Hepatology (1997) [Pubmed]
  5. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. Hagenbuch, B., Meier, P.J. J. Clin. Invest. (1994) [Pubmed]
  6. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Ho, R.H., Tirona, R.G., Leake, B.F., Glaeser, H., Lee, W., Lemke, C.J., Wang, Y., Kim, R.B. Gastroenterology (2006) [Pubmed]
  7. Molecular regulation of sinusoidal liver bile acid transporters during cholestasis. Gartung, C., Matern, S. The Yale journal of biology and medicine. (1997) [Pubmed]
  8. The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism. Eloranta, J.J., Jung, D., Kullak-Ublick, G.A. Mol. Endocrinol. (2006) [Pubmed]
  9. Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter. Shiao, T., Iwahashi, M., Fortune, J., Quattrochi, L., Bowman, S., Wick, M., Qadri, I., Simon, F.R. Genomics (2000) [Pubmed]
  10. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Mita, S., Suzuki, H., Akita, H., Hayashi, H., Onuki, R., Hofmann, A.F., Sugiyama, Y. Drug Metab. Dispos. (2006) [Pubmed]
  11. Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp. Anwer, M.S., Gillin, H., Mukhopadhyay, S., Balasubramaniyan, N., Suchy, F.J., Ananthanarayanan, M. J. Biol. Chem. (2005) [Pubmed]
  12. Novel bile acid derivatives (BANBs) with cytostatic activity obtained by conjugation of their side chain with nitrogenated bases. Vallejo, M., Castro, M.A., Medarde, M., Macias, R.I., Romero, M.R., El-Mir, M.Y., Monte, M.J., Briz, O., Serrano, M.A., Marin, J.J. Biochem. Pharmacol. (2007) [Pubmed]
  13. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Denson, L.A., Sturm, E., Echevarria, W., Zimmerman, T.L., Makishima, M., Mangelsdorf, D.J., Karpen, S.J. Gastroenterology (2001) [Pubmed]
  14. Cloning and expression of SLC10A4, a putative organic anion transport protein. Splinter, P.L., Lazaridis, K.N., Dawson, P.A., Larusso, N.F. World J. Gastroenterol. (2006) [Pubmed]
  15. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. McRae, M.P., Lowe, C.M., Tian, X., Bourdet, D.L., Ho, R.H., Leake, B.F., Kim, R.B., Brouwer, K.L., Kashuba, A.D. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  16. Enterohepatic bile salt transporters in normal physiology and liver disease. Kullak-Ublick, G.A., Stieger, B., Meier, P.J. Gastroenterology (2004) [Pubmed]
  17. Hepatobiliary transporter expression in human hepatocellular carcinoma. Zollner, G., Wagner, M., Fickert, P., Silbert, D., Fuchsbichler, A., Zatloukal, K., Denk, H., Trauner, M. Liver Int. (2005) [Pubmed]
  18. Disrupted coordinate regulation of farnesoid X receptor target genes in a patient with cerebrotendinous xanthomatosis. Honda, A., Salen, G., Matsuzaki, Y., Batta, A.K., Xu, G., Hirayama, T., Tint, G.S., Doy, M., Shefer, S. J. Lipid Res. (2005) [Pubmed]
  19. Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene. Jung, D., Hagenbuch, B., Fried, M., Meier, P.J., Kullak-Ublick, G.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  20. Molecular and functional characterization of bile acid transport in human hepatoblastoma HepG2 cells. Kullak-Ublick, G.A., Beuers, U., Paumgartner, G. Hepatology (1996) [Pubmed]
 
WikiGenes - Universities