Proteomics of Human Bile

  • Troels Zakarias Kristiansen
  • Anirban Maitra
  • Akhilesh Pandey

Abstract

Bile is an important body fluid with crucial functions ranging from fat absorption to excretion of metabolic breakdown products. Although the chemical composition of human bile is well understood, its protein constituents are beginning to be unravelled only recently. Here, we provide an overview of the proteomics of human bile, both in health and in diseases such as cholangiocarcinoma. A comprehensive catalog of proteins in the bile should facilitate better understanding of its role in physiology and the development and validation of biomarkers for hepatobiliary disorders.

Key Words

Bile LC-MS/MS proteomics biomarker discovery mass spectrometry hepatobiliary cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sherlock S, Dooley J. Diseases of the Liver and Biliary System, 11th ed. Malden, MA: Blackwell Science, 2002.Google Scholar
  2. 2.
    Clavien P-A, Baillie J. Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment. Malden, MA: Blackwell Science, 2001.Google Scholar
  3. 3.
    Guyton AC, Hall JE. Textbook of Medical Physiology, 10th ed. Philadelphia: Saunders, 2000.Google Scholar
  4. 4.
    Bittar EE. The Liver in Biology and Disease (principles of medical biology), Amsterdam: Elsevier Science, 2005.Google Scholar
  5. 5.
    Redinger RN. The coming of age of our understanding of the enterohepatic circulation of bile salts. Am J Surg 2003;185:168–172.PubMedCrossRefGoogle Scholar
  6. 6.
    Fuchs M. Bile acid regulation of hepatic physiology: III. Regulation of bile acid synthesis: past progress and future challenges. Am J Physiol Gastrointest Liver Physiol 2003;284:G551–G557.PubMedGoogle Scholar
  7. 7.
    Small DM, Dowling RH, Redinger RN. The enterohepatic circulation of bile salts. Arch Intern Med 1972;130:552–573.PubMedCrossRefGoogle Scholar
  8. 8.
    Arrese M, Ananthananarayanan M, Suchy FJ. Hepatobiliary transport: molecular mechanisms of development and cholestasis. Pediatr Res 1998;44:141–147.PubMedCrossRefGoogle Scholar
  9. 9.
    Arrese M, Trauner M. Molecular aspects of bile formation and cholestasis. Trends Mol Med 2003;9:558–564.PubMedCrossRefGoogle Scholar
  10. 10.
    Meier PJ, Stieger B. Bile salt transporters. Annu Rev Physiol 2002;64:635–661.PubMedCrossRefGoogle Scholar
  11. 11.
    Hagenbuch B, Meier PJ. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 2003;1609:1–18.PubMedCrossRefGoogle Scholar
  12. 12.
    Borst P, Elferink RO. Mammalian ABC transporters in health and disease. Annu Rev Biochem 2002;71:537–592.PubMedCrossRefGoogle Scholar
  13. 13.
    Mullock BM, Shaw LJ, Fitzharris B, et al. Sources of proteins in human bile. Gut 1985;26:500–509.PubMedCrossRefGoogle Scholar
  14. 14.
    Keulemans YC, Mok KS, deWit LT, Gouma DJ, Groen AK. Hepatic bile versus gallbladder bile: a comparison of protein and lipid concentration and composition in cholesterol gallstone patients. Hepatology 1998;28:11–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Coleman R. Biochemistry of bile secretion. Biochem J 1987;244:249–261.PubMedGoogle Scholar
  16. 16.
    Mullock BM, Dobrota M, Hinton RH. Sources of the proteins of rat bile. Biochim Biophys Acta 1978;543:497–507.PubMedGoogle Scholar
  17. 17.
    Reuben A. Biliary proteins. Hepatology 1984;4(5 Suppl):46S–50S.PubMedCrossRefGoogle Scholar
  18. 18.
    Sewell RB, Mao SJ, Kawamoto T, LaRusso NF. Apolipoproteins of high, low, and very low density lipoproteins in human bile. J Lipid Res 1983;24:391–401.PubMedGoogle Scholar
  19. 19.
    Albers CJ, Huizenga JR, Krom RA, Vonk RJ, Gips CH. Composition of human hepatic bile. Ann Clin Biochem 1985;22:129–132.PubMedGoogle Scholar
  20. 20.
    Gallinger S, Harvey PR, Petrunka CN, Ilson RG, Strasberg SM. Biliary proteins and the nucleation defect in cholesterol cholelithiasis. Gastroenterology 1987;92:867–875.PubMedGoogle Scholar
  21. 21.
    Yamazaki K, Powers SP, LaRusso NF. Biliary proteins: assessment of quantitative techniques and comparison in gallstone and nongallstone subjects. J Lipid Res 1988;29(8): 1055–1063.PubMedGoogle Scholar
  22. 22.
    Paul R, Sreekrishna K. Physicochemical and comparative studies on bile proteins. Indian J Biochem Biophys 1979;16:399–402.PubMedGoogle Scholar
  23. 23.
    Osnes T, Sandstad O, Skar V, Osnes M, Kierulf P. Total protein in common duct bile measured by acetonitrile precipitation and a micro bicinchoninic acid (BCA) method. Scand J Clin Lab Invest 1993;53:757–763.PubMedCrossRefGoogle Scholar
  24. 24.
    Reynoso-Paz S, Coppel RL, Mackay IR, Bass NM, Ansari AA, Gershwin ME. The immunobiology of bile and biliary epithelium. Hepatology 1999;30:351–357.PubMedCrossRefGoogle Scholar
  25. 25.
    vanEgmond M, Damen CA, vanSpriel AB, Vidarsson G, vanGarderen E, van deWinkel JG. IgA and the IgA Fc receptor. Trends Immunol 2001;22:205–211.PubMedCrossRefGoogle Scholar
  26. 26.
    Anderson NL, Polanski M, Pieper R, et al. The human plasma proteome: a nonredundant list developed by combination of four separate sources. Mol Cell Proteomics 2004;3:311–326.PubMedCrossRefGoogle Scholar
  27. 27.
    Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002;1:845–867.PubMedCrossRefGoogle Scholar
  28. 28.
    He C, Fischer S, Meyer G, Muller I, Jungst D. Two-dimensional electrophoretic analysis of vesicular and micellar proteins of gallbladder bile. J Chromatogr A 1997;776:109–115.PubMedCrossRefGoogle Scholar
  29. 29.
    Stark M, Jornvall H, Johansson J. Isolation and characterization of hydrophobic polypeptides in human bile. Eur J Biochem 1999;266:209–214.PubMedCrossRefGoogle Scholar
  30. 30.
    Jones JA, Kaphalia L, Treinen-Moslen M, Liebler DC. Proteomic characterization of metabolites, protein adducts, and biliary proteins in rats exposed to 1,1-dichloroethylene or diclofenac. Chem Res Toxicol 2003;16:1306–1317.PubMedCrossRefGoogle Scholar
  31. 31.
    deGroen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med 1999;341:1368–1378.PubMedCrossRefGoogle Scholar
  32. 32.
    Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transplant 2000;6 (6 Suppl 2):S30–S34.CrossRefGoogle Scholar
  33. 33.
    Bjornsson E, Kilander A, Olsson R. CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver 1999; 19:501–508.PubMedCrossRefGoogle Scholar
  34. 34.
    Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol 2000;95:204–207.PubMedCrossRefGoogle Scholar
  35. 35.
    Kristiansen TZ, Bunkenborg J, Gronborg M, et al. A proteomic analysis of human bile. Mol Cell Proteomics 2004;3:715–728.PubMedCrossRefGoogle Scholar
  36. 36.
    Modugno F. Ovarian cancer and high-risk women—implications for prevention, screening, and early detection. Gynecol Oncol 2003;91:15–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Haga Y, Sakamoto K, Egami H, Yoshimura R, Mori K, Akagi M. Clinical significance of serum CA125 values in patients with cancers of the digestive system. Am J Med Sci 1986;292:30–34.PubMedCrossRefGoogle Scholar
  38. 38.
    Chen CY, Shiesh SC, Tsao HC, Lin XZ. The assessment of biliary CA 125, CA 19-9 and CEA in diagnosing cholangiocarcinoma-the influence of sampling time and hepatolithiasis. Hepatogastroenterology 2002;49:616–620.PubMedGoogle Scholar
  39. 39.
    Ker CG, Chen JS, Lee KT, Sheen PC, Wu CC. Assessment of serum and bile levels of CA19-9 and CA125 in cholangitis and bile duct carcinoma. J Gastroenterol Hepatol 1991;6:505–508.PubMedGoogle Scholar
  40. 40.
    Brockmann J, Emparan C, Hernandez CA, et al. Gallbladder bile tumor marker quantification for detection of pancreato-biliary malignancies. Anticancer Res 2000;20:4941–4947.PubMedGoogle Scholar
  41. 41.
    Koopmann J, Thuluvath PJ, Zahurak ML, et al. Mac-2-binding protein is a diagnostic marker for biliary tract carcinoma. Cancer 2004; 101:1609–1615.PubMedCrossRefGoogle Scholar
  42. 42.
    Ping P, Vondriska TM, Creighton CJ, et al. A functional annotation of subproteomes in human plasma. Proteomics 2005;5:3506–3519.PubMedCrossRefGoogle Scholar
  43. 43.
    Omenn GS, States DJ, Adamski M, et al. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly available database. Proteomics 2005;5:3226–3245.PubMedCrossRefGoogle Scholar
  44. 44.
    Hay DW, Cahalane MJ, Timofeyeva N, Carey MC. Molecular species of lecithins in human gallbladder bile. J Lipid Res 1993;34:759–768.PubMedGoogle Scholar
  45. 45.
    Donovan JM, Jackson AA, Carey MC. Molecular species composition of intermixed micellar/vesicular bile salt concentrations in model bile: dependence upon hydrophilic-hydrophobic balance. J Lipid Res 1993;34:1131–1140.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2007

Authors and Affiliations

  • Troels Zakarias Kristiansen
    • 1
    • 2
  • Anirban Maitra
    • 3
  • Akhilesh Pandey
    • 4
  1. 1.McKusick-Nathans Institute of Genetic Medicine and Department of Biological ChemistryJohns Hopkins UniversityBaltimore
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Southern DenmarkOdense MDenmark
  3. 3.McKusick-Nathans Institute of Genetic Medicine, The Sol Goldman Pancreatic Cancer Research Center, and Departments of Biological Chemistry, Pathology and OncologyJohns Hopkins UniversityBaltimore
  4. 4.McKusick-Nathans Institute of Genetic Medicine, and Departments of Biological Chemistry, Oncology and PathologyJohns Hopkins UniversityBaltimore

Personalised recommendations