The Journal of Nutritional Biochemistry
Volume 21, Issue 3 , Pages 247-254 , March 2010

Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation

  • Stefania Cosentino

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • These authors contributed equally to the study.
    • ,
  • Claudia Gravaghi

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • Strang Cancer Research Laboratory, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA
    • These authors contributed equally to the study.
    • ,
  • Elena Donetti

      Affiliations

    • DMU, Department of Human Morphology, University of Milan, 20133 Milan, Italy
    • ,
  • Bianca M. Donida

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • ,
  • Giovanni Lombardi

      Affiliations

    • IRCCS Istituto Ortopedico Galeazzi, 20133 Milan, Italy
    • ,
  • Marzia Bedoni

      Affiliations

    • DMU, Department of Human Morphology, University of Milan, 20133 Milan, Italy
    • Fondazione Don Gnocchi ONLUS, Polo Tecnologico 20148 Milan, Italy
    • ,
  • Amelia Fiorilli

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • ,
  • Guido Tettamanti

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • ,
  • Anita Ferraretto

      Affiliations

    • Department of Medical Chemistry, Biochemistry and Biotechnology, LITA Segrate, University of Milan, 20090, Milan, Italy
    • Corresponding Author InformationCorresponding author. Tel: +39 0250330341; fax: +39 0250230365.

Received 29 July 2008 ,Revised 16 November 2008 ,Accepted 15 December 2008.

References 

  1. Meisel H, Günther S. Food proteins as precursors of peptides modulating human cell activity. Nahrung. 1998;42:175–176
  2. FitzGerald RJ. Potential uses of caseinophosphopeptides. Int Dairy J. 1998;8:451–457
  3. Erba D, Ciappellano S, Testolin G. Effect of the ratio of casein phosphopeptides to calcium (w/w) on passive calcium transport in the distal small intestine of rats. Nutrition. 2002;18:743–746
  4. Mykkänen HM, Wasserman RH. Enhanced absorption of calcium by casein phosphopeptides in rachitis and normal chicks. J Nutr. 1980;119:2141–2148
  5. Erba D, Ciappellano S, Testolin G. Effect of caseinphosphopeptides on inhibition of calcium intestinal absorption due to phosphate. Nutr Res. 2001;21:649–656
  6. Lee YS, Noguchi T, Naito H. Intestinal absorption of calcium in rats given diets containing casein or aminoacid mixture: the role of casein phosphopeptides. Br J Nutr. 1983;49:67–76
  7. Sato R, Noguchi T, Naito H. Casein phopshopeptides (CPP) enhances calcium absorption from the ligated segment of rat small intestine. J Nutr Sci Vitaminol. 1986;32:67–76
  8. Kitts DD, Yuan YV, Nagasawa T, Moriyama Y. Effect of casein, caseinphosphopeptides and calcium intake on ileal 45Ca disappearance and temporal systolic blood pressure in spontaneously hypertensive rats. Br J Nutr. 1992;69:765–781
  9. Brommage R, Juillerat MA, Jost R. Influence of casein phosphopeptides and lactulose on intestinal calcium absorption in adult female rats. Lait. 1991;71:173–180
  10. Kopra N, Scholz-Ahrens KE, Barth CA. Effect of casein phosphopeptides on utilisation of calcium in vitamin D-deficient rats. Milchwissenschaft. 1992;47:488–492
  11. Bennet T, Desmond A, Harrington M, McDonagh D, FitzGerald R, Flyn A, et al. The effect of high intakes of casein and casein phosphopeptide on calcium absorption in the rat. Br J Nutr. 2000;83:673–680
  12. Mellander O. The physiological importance of the casein phosphopeptide calcium salts. II Peroral calcium dosage of infants. Acta Soc Med Ups. 1950;55:247–255
  13. Heaney RP, Saito Y, Orimo H. Effect of casein phosphopeptide on absorbability of co-ingested calcium in normal post menopausal women. J Bone Miner Metab. 1994;12:77–81
  14. Hansen M, Sandstrőm B, Jensen M, Sorensen SS. Casein phosphopeptides improve zinc and calcium absorption from rice-based but not from whole-grain infant cereal. J Pediatr Gastroenterol Nutr. 1997;24:56–62
  15. Hansen M, Sandstrőm B, Jensen M, Sorensen SS. Effect of casein phosphopeptides on zinc and calcium absorption from bread meals. J Trace Elem Med Biol. 1997;11:143–149
  16. Lopez-Huertas E, Teucher B, Boza JJ, Martinez-Ferez A, Majsak-Newman G, Baro L, et al. Absorption of calcium from milks enriched with fructo-oligosaccharides, caseinophosphopeptides, tricalcium phosphate and milk solids. Am J Clin Nutr. 2006;83:310–316
  17. Narva M, Kärkkäinen M, Poussa T, Lamberg-Allardt C, Korpela R. Casein phosphopeptides in milk and fermented milk do not affect calcium metabolism acutely in post menopausal women. J Am Coll Nutr. 2003;22:88–93
  18. Teucher B, Majsak-Newman G, Dainty JR, McDonagh D, FitzGerald RJ, Fairweather-Tait S. Calcium absorption is not increased by caseinophosphopeptides. Am J Clin. 2006;84:162–166
  19. Holt C. Structure and stability of bovine casein micelles. Adv Protein Chem. 1992;43:63–151
  20. Holt C, De Kruiff CG, Tuinier R, Timmins PA. Substructure of bovine casein micelles by small-angle X-ray and neutron scattering. Colloids Surf. 2003;213:275–284
  21. Rollema HS. Casein association and micelle formation. In:  Fox PF editors. Advanced dairy chemistry. vol. 1: Proteins:London: Elsevier Applied Science; 1992;p. 111–140
  22. Little FM, Holt C. An equilibrium thermodynamic model of the sequestration of calcium phosphate by casein phosphopeptides. Eur Biophys J. 2004;33:435–447
  23. Cross KJ, Huq LN, Palamara JE, Perich JW, Reynolds EC. Physicochemical characterization of casein phosphopeptide-amorphous calcium phosphate nanocomplexes. J Biol Chem. 2005;280:15362–15369
  24. Holt C, Wahlgren MN, Drakenberg T. Ability of a β-casein phosphopeptide to modulate the precipitation of calcium phosphate by forming amorphous dicalcium phosphate nanoclusters. Biochem J. 1996;314:1035–1039
  25. Holt C, Timmins PA, Errington N, Leaver J. A core-shell model of calcium phosphate nanoclusters stabilized by β-casein phosphopeptides, derived from sedimentation equilibrium and small-angle X-ray and neutron-scattering measurements. Eur J Biochem. 1998;252:73–78
  26. Ferraretto A, Signorile A, Gravaghi C, Fiorilli A, Tettamanti G. Casein phosphopeptides influence calcium uptake by cultured human intestinal HT-29 tumor cells. J Nutr. 2001;131:1655–1661
  27. Ferraretto A, Gravaghi C, Fiorilli A, Tettamanti G. Casein-derived bioactive phosphopeptides. Role of phosphorylation and primary structure in promoting calcium uptake by HT-29 tumor cells. FEBS Lett. 2003;551:92–98
  28. Gravaghi C, Del Favero E, Cantu L, Donetti E, Bedoni M, Fiorilli A, et al. Casein phosphopeptide promotion of calcium uptake in HT-29 cells: relationship between biological activity and supramolecular structure. FEBS J. 2007;274:4999–5011
  29. Zweibaum A, Laburthe M, Grasset E, Louvard D. In:  Rauner BB,  Field M,  Frizzel RA,  Schultz SG editor. Handbook of Physiology. 4th ed.. Bethesda, MD: Journals of the American Physical Society; 1991;p. 223–255
  30. Halline AG, Davidson NO, Skarosi SF, Sitrin MD, Tietze C, Alpers DH, et al. Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of Caco-2 cells. Endocrinology. 1994;134:1710–1717
  31. Vanderwalle B, Wattez N, Lefebvre J. Effects of vitamin D3 derivatives on growth, differentiation and apoptosis in tumoral colonic HT-29 cells: possible implication of intracellular calcium. Cancer Lett. 1995;97:99–106
  32. Polak-Charcon S, Hekmati M, Ben-Shaul Y. The effect of modifying the culture medium on cell polarity in a human colon carcinoma cell line. Cell Differ. 1989;26:119–129
  33. Ferraretto A, Gravaghi C, Donetti E, Cosentino S, Donida BM, Bedoni M, et al. New methodological approach to induce a differentiation phenotype in Caco-2 cells prior to post-confluence stage. Anticancer Res. 2007;27:3919–3926
  34. Brehier A, Thomasset M. Human colon cell line HT-29: characterization of 1,25-dihydroxyvitamin D3 receptor and induction of differentiation by the hormone. J Steroid Biochem. 1988;29:265–270
  35. Buras RR, Shabahang M, Davoodi F, Schumaker LM, Cullen KJ, Byers S, et al. The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation. Cell Prolif. 1995;28:245–262
  36. Messer M, Dahlquist A. A one-step ultramicro method for the assay of intestinal disaccharidases. Anal Biochem. 1966;14:376–392
  37. Lowry OH, Rosebrough N, Farr A, Randall R. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–275
  38. Tsien RY, Poenie GM. Fluorescence ratio imaging: a new window into intracellular ionic signalling. Trends Biochem Sci. 1986;11:450–455
  39. Grynkiewicz G, Poenie GM, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985;260:3440–3450
  40. Harper KD, Iozzo RV, Haddad JG. Receptors for and bio responses to 1,25-dihydroxyvitamin D in a human colon carcinoma cell line (HT-29). Metabolism. 1989;38:1062–1069
  41. Rousset M, Chevalier G, Rousset JP, Dussaulx E, Zweibaum A. Presence and cell growth-related variations of glycogen in human colorectal adenocarcinoma cell lines in culture. Cancer Res. 1979;39:531–534
  42. Lesuffleur T, Barbat A, Dassulx E, Zweibaum A. Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells. Cancer Res. 1990;50:6334–6343
  43. Wikman-Larhed A, Artursson P. Co-cultures of human intestinal goblet (HT29-H) and absorptive (Caco-2) cells for studies of drug and peptide absorption. Eur J Pharm Sci. 1995;3:171–183
  44. Pàcha J. Development of intestinal transport function in mammals. Physiol Rev. 2000;80:1633–1667
  45. Suzuki T, Hara H. Various nondigestible saccharides open a paracellular calcium transport pathway with the induction of intracellular calcium signaling in human intestinal Caco-2 cells. J Nutr. 2004;134:1935–1941
  46. Shamay A, Shapiro F, Mabjeesh SJ, Silanikove N. Casein-derived phosphopeptides disrupt tight junction integrity, and precipitously dry up milk secretion in goats. Life Sci. 2002;70:2707–2719
  47. Bronner F, Pansu D, Stein WD. Analysis of intestinal calcium transport across the intestine. Am J Physiol. 1986;250:G561–G569
  48. Kawahara M, Kuroda Y, Arispe N, Rojas E. Alzheimer's b-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by common mechanism in a hypothalamic GnRH neuronal cell line. J Biol Chem. 2000;275:14077–14083
  49. Ramasamy I. Recent advances in physiological calcium homeostasis. Clin Chem Lab Med. 2006;44:237–273
  50. Conigrave AD, Quinn SJ, Brown EM. L-Amino acid sensing by the extracellular Ca2+-sensing receptor. PNAS. 2000;97:4814–4819
  51. Gama L, Baxendale-Cox L, Breitwieser GE. Ca2+ sensing receptors in intestinal epithelium. Am J Physiol (Cell Physiol). 1997;273:C1168–C1175
  52. Chakrabarty S, Wang H, Canaff L, Hendy GN, Appelman H, Varani J. Calcium sensing receptors in human colon carcinoma: interaction with Ca2+ and 1,25-dihydroxyvitamin D3. Cancer Res. 2005;65:493–498
  53. Taparia S, Fleet JC, Peng JB, Wang XD, Wood RJ. 1,25-Dihydroxyvitamin D and 25 hydroxyvitamin D-mediated regulation of TRPV6 (a putative epithelial calcium channel) mRNA expression in Caco-2 cells. Eur J Nutr. 2006;45:196–204
  54. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006;147:5542–5548
  55. Leipziger J, Fischer KG, Greger R. Voltage-dependent Ca2+ influx in the epithelial cell line HT-29: simultaneous use of intracellular Ca2+ measurements and nystatin perforated patch-clamp technique. Eur J Physiol. 1994;426:427–432
  56. Ekmekcioglu C. A physiological approach for preparing and conducting intestinal bioavailability studies using experimental systems. Food Chem. 2002;76:225–230
  57. Khanal R, Nemere I. Regulation of intestinal calcium transport. Annu Rev Nutr. 2008;28:179–196
  58. Grau MV, Baron JA, Sandler RS, Haile RW, Beach ML, Church TR, et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst. 2003;95:1765–1771
  59. Sitrin MD, Bissonnette M, Bolt MJG, Wali R, Khare S, Scaglione-Sewell B, et al. Rapid effects of 1,25 (OH)2 vitamin D3 on signal transduction systems in colonic cells. Steroids. 1999;64:137–142

☆ This work was supported in part by the EU FAIR Programme Project CT98-3077 (“Caseinphosphopeptide (CPP): Nutraceutical/functional food ingredients for food and pharmaceutical applications”) and by Fondazione Romeo and Enrica Invernizzi (“CPP: role in the calcium intestinal absorption and its utilization. A perspective study on their possible usage as nutraceuticals or functional food to favour calcium bioavailability”).

PII: S0955-2863(09)00002-3

doi: 10.1016/j.jnutbio.2008.12.016

The Journal of Nutritional Biochemistry
Volume 21, Issue 3 , Pages 247-254 , March 2010

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