Skip to main content
Log in

Regulation of the ileal bile acid-binding protein gene: An approach to determine its physiological function(s)

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Ileal bile acid-binding protein (I-BABP) is a soluble bile acids (BA) carrier protein which belongs to the fatty acid-binding protein (FABP) family. In the gut, its expression is strictly restricted to the ileum, where it is thought to be involved in the active BA reabsorption. Therefore, I-BABP gene expression levels might be rate limiting for the BA enterohepatic circulation, and hence, might be crucial for cholesterol (CS) homeostasis. Indeed, BA not reclaimed by intestinal absorption constitute the main way to eliminate a CS excess. However, such a function is not yet established. Because generally rate limiting genes are tightly controlled, we have undertaken the study of the I-BABP gene regulation. It was found that both BA and CS, probably via oxysterols, are able to up-regulate the trancription rate of I-BABP gene. The fact that intracellular sterol sensors (FXR, LXR and SREBP1c) are involved in the control of I-BABP gene expression strongly suggest a crucial role for I-BABP in the ileum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Russell DW, Setchell KD: Bile acid biosynthesis. Biochemistry 31: 4737–4749, 1992

    Google Scholar 

  2. Kramer W, Girbig F, Gutjahr U, Kowalewski S, Jouvenal K, Muller G, Tripier D, Wess G: Intestinal bile acid absorption. Na(+)-dependent bile acid transport activity in rabbit small intestine correlates with the coexpression of an integral 93-kDa and a peripheral 14-kDa bile acid-binding membrane protein along the duodenumileum axis. J Biol Chem 268: 18035–18046, 1993

    Google Scholar 

  3. Saeki T, Matoba K, Furukawa H, Kirifuji K, Kanamoto R, Iwami K: Characterization, cDNA cloning, and functional expression of mouse ileal sodium-dependent bile acid transporter. J Biochem 125: 846–851, 1999

    Google Scholar 

  4. Veerkamp JH, Maatman RG: Cytoplasmic fatty acid-binding proteins: Their structure and genes. Prog Lipid Res 34: 17–52, 1995

    Google Scholar 

  5. Weinberg SL, Burckhardt G, Wilson FA: Taurocholate transport by rat intestinal basolateral membrane vesicles. Evidence for the presence of an anion exchange transport system. J Clin Invest 78: 44–50, 1986

    Google Scholar 

  6. Abe T, Kakyo M, Sakagami H, Tokui T, Nishio T, Tanemoto M, Nomura H, Hebert SC, Matsuno S, Kondo H, Yawo H: Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2. J Biol Chem 273: 22395–22401, 1998

    Google Scholar 

  7. Inokuchi A, Hinoshita E, Iwamoto Y, Kohno K, Kuwano M, Uchiumi T: Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes: A transcriptional control of a plausible bile acid transporter. J Biol Chem 2001 (in press)

  8. Gantz I, Nothwehr SF, Lucey M, Sacchettini JC, DelValle J, Banaszak LJ, Naud M, Gordon JI, Yamada T: Gastrotropin: Not an enterooxyntin but a member of a family of cytoplasmic hydrophobic ligand binding proteins. J Biol Chem 264: 20248–20254, 1989

    Google Scholar 

  9. Sacchettini JC, Hauft SM, Van Camp SL, Cistola DP, Gordon JI: Developmental and structural studies of an intracellular lipid binding protein expressed in the ileal epithelium. J Biol Chem 265: 19199–19207, 1990

    Google Scholar 

  10. Amano O, Kanda T, Ono T, Iseki S: Immunocytochemical localization of rat intestinal 15 kDa protein, a member of cytoplasmic fatty acid-binding proteins. Anat Rec 234: 215–222, 1992

    Google Scholar 

  11. Stengelin S, Apel S, Becker W, Maier M, Rosenberger J, Bewersdorf U, Girbig F, Weyland C, Wess G, Kramer W: The rabbit ileal lipid-binding protein. Gene cloning and functional expression of the recombinant protein. Eur J Biochem 239: 887–896, 1996

    Google Scholar 

  12. Fujita M, Fujii H, Kanda T, Sato E, Hatakeyama K, Ono T: Molecular cloning, expression, and characterization of a human intestinal 15-kDa protein. Eur J Biochem 233: 406–413, 1995

    Google Scholar 

  13. Walz DA, Wider MD, Snow JW, Dass C, Desiderio DM: The complete amino acid sequence of porcine gastrotropin, an ileal protein which stimulates gastric acid and pepsinogen secretion. J Biol Chem 263: 14189–14195, 1988

    Google Scholar 

  14. Alpini G, Glaser SS, Rodgers R, Phinizy JL, Robertson WE, Lasater J, Caligiuri A, Tretjak Z, LeSage GD: Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes. Gastroenterology 113: 1734–1740, 1997

    Google Scholar 

  15. Watanabe K, Hoshi N, Tsuura Y, Kanda T, Fujita M, Fujii H, Ono T, Suzuki T: Immunohistochemical distribution of intestinal 15 kDa protein in human tissues. Arch Histol Cytol 58: 303–306, 1995

    Google Scholar 

  16. Iseki S, Amano O, Kanda T, Fujii H, Ono T: Expression and localization of intestinal 15 kDa protein in the rat. Mol Cell Biochem 123: 113–120, 1993

    Google Scholar 

  17. Crossman MW, Hauft SM, Gordon JI: The mouse ileal lipid-binding protein gene: A model for studying axial patterning during gut morphogenesis. J Cell Biol 126: 1547–1564, 1994

    Google Scholar 

  18. Gong YZ, Kato T, Schwartz DA, Norris JS, Wilson FA: Ontogenic and glucocorticoid-accelerated expression of rat 14 kDa bile acidbinding protein. Anat Rec 245: 532–538, 1996

    Google Scholar 

  19. Hwang ST, Henning SJ: Hormonal regulation of expression of ileal bile acid binding protein in suckling rats. Am J Physiol Regul Integr Comp Physiol 278: R1555–R1563, 2000

    Google Scholar 

  20. Lucke C, Zhang F, Ruterjans H, Hamilton JA, Sacchettini JC: Flexibility is a likely determinant of binding specificity in the case of ileal lipid binding protein. Structure 4: 785–800, 1996

    Google Scholar 

  21. Lucke C, Zhang F, Hamilton JA, Sacchettini JC, Ruterjans H: Solution structure of ileal lipid binding protein in complex with glycocholate. Eur J Biochem 267: 2929–2938, 2000

    Google Scholar 

  22. Kramer W, Sauber K, Baringhaus KH, Kurz M, Stengelin S, Lange G, Corsiero D, Girbig F, Konig W, Weyland C: Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinity labeling, matrix-assisted laser desorption ionizationmass spectrometry, and nmr structure. J Biol Chem 276: 7291–7301, 2001

    Google Scholar 

  23. Miller KR, Cistola DP: Titration calorimetry as a binding assay for lipid-binding proteins. Mol Cell Biochem 123: 29–37, 1993

    Google Scholar 

  24. Kramer W, Corsiero D, Friedrich M, Girbig F, Stengelin S, Weyland C: Intestinal absorption of bile acids: Paradoxical behaviour of the 14 kDa ileal lipid-binding protein in differential photoaffinity labelling. Biochem J 333: 335–341, 1998

    Google Scholar 

  25. Kanda T, Niot I, Foucaud L, Fujii H, Bernard A, Ono T, Besnard P: Effect of bile on the intestinal bile-acid binding protein (IBABP) expression. In vitro and in vivo studies. FEBS Lett 384: 131–134, 1996

    Google Scholar 

  26. Kanda T, Foucand L, Nakamura Y, Niot I, Besnard P, Fujita M, Sakai Y, Hatakeyama K, Ono T, Fujii H: Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells. Biochem J 330: 261–265, 1998

    Google Scholar 

  27. Escher P, Wahli W: Peroxisome proliferator-activated receptors: Insight into multiple cellular functions. Mutat Res 448: 121–138, 2000

    Google Scholar 

  28. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM: Bile acids: Natural ligands for an orphan nuclear receptor. Science 284: 1365–1368, 1999

    Google Scholar 

  29. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B: Identification of a nuclear receptor for bile acids. Science 284: 1362–1365, 1999

    Google Scholar 

  30. Wang H, Chen J, Hollister K, Sowers LC, Forman BM: Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3: 543–553, 1999

    Google Scholar 

  31. Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW et al.: Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81: 687–693, 1995

    Google Scholar 

  32. Grober J, Zaghini I, Fujii H, Jones SA, Kliewer SA, Willson TM, Ono T, Besnard P: Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid x receptor/9-cis-retinoic acid receptor heterodimer. J Biol Chem 274: 29749–29754, 1999

    Google Scholar 

  33. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ: Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102: 731–744, 2000

    Google Scholar 

  34. Shimano H: Sterol regulatory element-binding proteins (SREBPs): Transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40: 439–452, 2001

    Google Scholar 

  35. Zaghini I, Landrier JF, Grober J, Krief S, Jones SA, Monnot MC, Lefrere I, Watson MA, Collins JL, Fujii H, Besnard P: Sterol regulatory element-binding protein-1c is responsible for cholesterol regulation of ileal bile-acid binding protein gene in vivo. 2001 (submitted)

  36. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ: Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14: 2819–2830, 2000

    Google Scholar 

  37. DeBose-Boyd RA, Ou J, Goldstein JL, Brown MS: Expression of sterol regulatory element-binding protein 1c (SREBP-1c) mRNA in rat hepatoma cells requires endogenous LXR ligands. Proc Natl Acad Sci USA 98: 1477–1482, 2001

    Google Scholar 

  38. Yoshikawa T, Shimano H, Amemiya-Kudo M, Yahagi N, Hasty AH, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Kimura S, Ishibashi S, Yamada N: Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol Cell Biol 21: 2991–3000, 2001

    Google Scholar 

  39. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ: Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 6: 507–515, 2000

    Google Scholar 

  40. Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, Galardi C, Wilson JG, Lewis MC, Roth ME, Maloney PR, Willson TM, Kliewer SA: A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 6: 517–526, 2000

    Google Scholar 

  41. Schwartz K, Lawn RM, Wade DP: ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. Biochem Biophys Res Commun 274: 794–802, 2000

    Google Scholar 

  42. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, Mangelsdorf DJ: Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289: 1524–1529, 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Landrier, JF., Grober, J., Zaghini, I. et al. Regulation of the ileal bile acid-binding protein gene: An approach to determine its physiological function(s). Mol Cell Biochem 239, 149–155 (2002). https://doi.org/10.1023/A:1020557502795

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020557502795

Navigation