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Slc10a2  -  solute carrier family 10 (sodium/bile acid...

Rattus norvegicus

Synonyms: ASBT, Apical sodium-dependent bile acid transporter, IBAT, ISBT, Ileal Na(+)/bile acid cotransporter, ...
 
 
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Disease relevance of Slc10a2

  • RESULTS: Indomethacin-induced ileitis in Lewis rats leads to specific reductions in ileal ASBT messenger RNA and protein levels, whereas c-jun and c-fos are induced [1].
  • Massive intestinal resection resulted in ileal hypertrophy and an apparently maladaptive specific down-regulation in ASBT protein expression [2].
  • Surgical reduction of IBAT resulted in hypertrophy of WAT and an improved efficiency of weight gain, whereas body composition, WAT cellularity, and the efficiency of weight gain of similarly operated rats fed stock diet were unaltered from those of unoperated animals fed stock diet [3].
  • Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22 and inhibited IBAT 5'D [4].
  • These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism [5].
 

High impact information on Slc10a2

  • Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum [6].
  • Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT [6].
  • Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes [6].
  • Jejunal and ileal luminal BAs, portal blood BAs, and messenger RNA and protein for the apical sodium-dependent bile acid transporter, the ileal bile acid binding protein, and the heteromeric organic solute transporter (Ostalpha/Ostbeta)were evaluated [7].
  • RESULTS: In Caco-2 cells, ASBT messenger RNA expression was reduced 65% after interleukin-1beta treatment, while c-fos and c-jun were up-regulated 2-fold [8].
 

Chemical compound and disease context of Slc10a2

  • Propranolol or hexamethonium injected i.v. during the steady state hyperthermia resulted in a rapid drop in IBAT temperature and in a reversal of the gradient between IBAT and colonic temperature both in denervated and in intact IBAT [9].
 

Biological context of Slc10a2

 

Anatomical context of Slc10a2

  • Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and (3)H-TC uptake in purified cholangiocytes [13].
  • CONCLUSION: These data demonstrate that expression of ASBT and t-ASBT in cholangiocytes is regulated by a negative feedback loop while the expression of these transporters in terminal ileum is modified via positive feedback [14].
  • Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains unclear [14].
  • METHODS: ASBT regulation was studied in IL-1beta-treated IEC-6 and Caco-2 cells and in indomethacin-treated rats [1].
  • Rat ASBT promoter transgenic, wild-type, and c-fos-null mice were treated with indomethacin to assess the response to acute inflammation of the ileal mucosa [8].
 

Associations of Slc10a2 with chemical compounds

  • We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity [13].
  • Bile acid transport by cholangiocyte ASBT can contribute to hepatobiliary secretion in vivo [13].
  • RESULTS: In cholangiocytes, both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet [14].
  • Treatment with MG-132, a proteasome inhibitor, causes time-dependent increased ASBT levels and increased intracellular accumulation of ASBT [12].
  • Previous studies (Sung, A.-Q., Arresa, M. A., Zeng, L., Swaby, I'K., Zhou, M. M., and Suchy, F. J. (2001) J. Biol. Chem. 276, 6825-6833) from our laboratory demonstrated that rat Asbt follows an apical sorting pathway that is brefeldin A-sensitive and insensitive to protein glycosylation, monensin treatment, and low temperature shift [15].
 

Regulatory relationships of Slc10a2

  • We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores [13].
 

Other interactions of Slc10a2

 

Analytical, diagnostic and therapeutic context of Slc10a2

  • METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair-fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets, were assessed by both quantitative RNase protection assays and quantitative immunoblotting [14].
  • Indirect immunofluorescence studies localized the ASBT protein to the apical membrane of the renal proximal convoluted tubule [11].
  • Northern and Western blotting revealed both the ASBT mRNA and protein in rat kidney [11].
  • In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes [6].
  • Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver [6].

References

  1. Inflammatory-mediated repression of the rat ileal sodium-dependent bile acid transporter by c-fos nuclear translocation. Chen, F., Ma, L., Sartor, R.B., Li, F., Xiong, H., Sun, A.Q., Shneider, B. Gastroenterology (2002) [Pubmed]
  2. Analysis of the effect of intestinal resection on rat ileal bile Acid transporter expression and on bile Acid and cholesterol homeostasis. Al-Ansari, N., Xu, G., Kollman-Bauerly, K., Coppola, C., Shefer, S., Ujhazy, P., Ortiz, D., Ma, L., Yang, S., Tsai, R., Salen, G., Vanderhoof, J., Shneider, B.L. Pediatr. Res. (2002) [Pubmed]
  3. Effect of cafeteria feeding on brown and white adipose tissue cellularity, thermogenesis, and body composition in rats. Tulp, O.L., Frink, R., Danforth, E. J. Nutr. (1982) [Pubmed]
  4. Inhibition of iodothyronine 5'-deiodinase by iopanoic acid does not block nuclear T3 accumulation during rat fetal development. Tuca, A., Giralt, M., Villarroya, F., Viñas, O., Mampel, T., Iglesias, R. Pediatr. Res. (1994) [Pubmed]
  5. Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats. Bartness, T.J., Wade, G.N. Behav. Neurosci. (1984) [Pubmed]
  6. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter. Lazaridis, K.N., Pham, L., Tietz, P., Marinelli, R.A., deGroen, P.C., Levine, S., Dawson, P.A., LaRusso, N.F. J. Clin. Invest. (1997) [Pubmed]
  7. Bile acids induce ileal damage during experimental necrotizing enterocolitis. Halpern, M.D., Holubec, H., Saunders, T.A., Dvorak, K., Clark, J.A., Doelle, S.M., Ballatori, N., Dvorak, B. Gastroenterology (2006) [Pubmed]
  8. c-Fos is a critical mediator of inflammatory-mediated repression of the apical sodium-dependent bile acid transporter. Neimark, E., Chen, F., Li, X., Magid, M.S., Alasio, T.M., Frankenberg, T., Sinha, J., Dawson, P.A., Shneider, B.L. Gastroenterology (2006) [Pubmed]
  9. Prepontine knife cut-induced hyperthermia in the rat. Effect of chemical sympathectomy and surgical denervation of brown adipose tissue. Benzi, R.H., Shibata, M., Seydoux, J., Girardier, L. Pflugers Arch. (1988) [Pubmed]
  10. The role of AP-1 in the transcriptional regulation of the rat apical sodium-dependent bile acid transporter. Chen, F., Ma, L., Al-Ansari, N., Shneider, B. J. Biol. Chem. (2001) [Pubmed]
  11. Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum. Christie, D.M., Dawson, P.A., Thevananther, S., Shneider, B.L. Am. J. Physiol. (1996) [Pubmed]
  12. Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes. Xia, X., Roundtree, M., Merikhi, A., Lu, X., Shentu, S., Lesage, G. J. Biol. Chem. (2004) [Pubmed]
  13. Secretin activation of the apical Na+-dependent bile acid transporter is associated with cholehepatic shunting in rats. Alpini, G., Glaser, S., Baiocchi, L., Francis, H., Xia, X., Lesage, G. Hepatology (2005) [Pubmed]
  14. Differential expression of cholangiocyte and ileal bile acid transporters following bile acid supplementation and depletion. Kip, N.S., Lazaridis, K.N., Masyuk, A.I., Splinter, P.L., Huebert, R.C., LaRusso, N.F. World J. Gastroenterol. (2004) [Pubmed]
  15. Association of the 16-kDa subunit c of vacuolar proton pump with the ileal Na+-dependent bile acid transporter: protein-protein interaction and intracellular trafficking. Sun, A.Q., Balasubramaniyan, N., Liu, C.J., Shahid, M., Suchy, F.J. J. Biol. Chem. (2004) [Pubmed]
  16. Molecular analysis of the adaptive response of intestinal bile acid transport after ileal resection in the rat. Coppola, C.P., Gosche, J.R., Arrese, M., Ancowitz, B., Madsen, J., Vanderhoof, J., Shneider, B.L. Gastroenterology (1998) [Pubmed]
 
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