Skip to main content
SpringerLink
Log in

Enhanced expression of α1-acid glycoprotein and fucosylation in hepatitis B patients provides an insight into pathogenesis

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Altered glycosylation and concentration of α1-acid glycoprotein has been known to be related to the pathogenesis of the hepatic diseases. The present study investigated enhanced fucosylation of AGP in the sera of chronic hepatitis B (HBV-CH) and hepatitis B cirrhosis (HBV-LC) patients by high performance anion exchange chromatography and by ELISA using fucose binding Aleuria aurantia lectin. The concentration of AGP determined by ELISA using monoclonal anti-human AGP (mAb-AGP) showed high level of AGP in HBV-CH and HBV-LC patients. This was further judged by association constant (K A) measured by surface plasmon resonance analysis. There was no apparent linkage variation of sialic acid among different patient groups when tested with two sialic acid binding lectins viz., Maackia amurensis agglutinin (MAA, NeuAc α2-3-) and Sambucus nigra agglutinin (SNA, NeuAc α2-6-) respectively. There was no change of oligosaccharide branching in HBV-CH in comparison to controls whereas a slight change was observed in HBV-LC using ConA. The above results suggest that the changes in concentration of AGP and fucosylation have a prognostic value of hepatitis diseases and it could be possible to use AGP as diagnostic marker besides clinical examination and routine laboratory investigation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

AAL:

Aleuria aurantia lectin

AGP:

α1-Acid glycoprotein

HBV:

Hepatitis B virus

HBV-CH:

Chronic viral hepatitis B

HBV-LC:

Viral hepatitis B cirrhosis

HCC:

Hepatocellular carcinoma

HPAEC-PAD:

High performance anion exchange chromatography pulse amperometric detection

MAA:

Maackia amurensis agglutinin

SD:

Standard deviation

SNA:

Sambucus nigra agglutinin

SPR :

Surface plasmon resonance

References

  1. Schmid, K., Nimerg, R.B., Kimura, A., Yamaguchi, H., Binette, J.P.: The carbohydrate units of human alpha 1-acid glycoprotein. Biochim. Biophys. Acta 492, 291–302 (1977)

    CAS  PubMed  Google Scholar 

  2. Kushner, I., Mackiewicz, A.: In: Mackiewicz, A., Kushner, I., Baumann, H. (eds.) Acute Phase Proteins: Molecular Biology, Biochemistry and Clinical Applications, pp. 4–19. CRC, Boca Raton (1993)

    Google Scholar 

  3. Bierhuizen, M.F.A., Wit, M.D., Govers, C.A.R.L., Ferwerda, W., Koeleman, C., Pos, O., Dijk, W.V.: Glycosylation of three molecular forms of human α1-acid glycoprotein having different interactions with concanavalin A. Variations in the occurrence of di-, tri-, and tetraantennary glycans and the degree of sialylation. Eur. J. Biochem. 175, 387–394 (1988). doi:10.1111/j.1432-1033.1988.tb14208.x

    Article  CAS  PubMed  Google Scholar 

  4. Van Dijk, W., Havenaar, E.C., Brinkman-van der Linden, E.C.M.: Alpha1-acid glycoprotein (orosomucoid): pathophysiological changes in glycosylation in relation to its function. Glycoconj. J. 12, 227–233 (1995). doi:10.1007/BF00731324

    Article  PubMed  Google Scholar 

  5. Hansen, J.E., Larsen, V.A., Bog-Hansen, T.C.: The microheterogeneity of α1-acid glycoprotein in inflammatory lung disease, cancer of the lung and normal health. Clin. Chim. Acta 38, 41–47 (1984). doi:10.1016/0009-8981(84)90352-8

    Article  Google Scholar 

  6. Hrycaj, P., Sobieska, M., Mackiewicz, S., Muller, W.: Microheterogenicity of alpha 1-acid glycoprotein in early and established rheumatoid arthritis. J. Rheumatol. 20, 2020–2024 (1993)

    CAS  PubMed  Google Scholar 

  7. Mackiewicz, A., Mackiewicz, K.: Glycoforms of serum α1 acid glycoprotein as markers of inflammation and cancer. Glycoconj. J. 12, 241–247 (1995). doi:10.1007/BF00731326

    Article  CAS  PubMed  Google Scholar 

  8. Brinkman-Van der Linden, E.C.M., Havenaar, E.C., Van Ommen, E.C.R., Van Kamp, G.J., Gooren, L.J.G., Van Dijk, W.: Oral estrogen treatment induces a decrease in expression of sialyl Lewisx on α1-acid glycoprotein in females and male-to-female transsexuals. Glycobiology 6, 407–412 (1996). doi:10.1093/glycob/6.4.407

    Article  CAS  PubMed  Google Scholar 

  9. Shiyan, S.D., Bovin, N.V.: Carbohydrate composition and immunomodulator activity of different glycoforms of alpha 1-acid glycoprotein. Glycoconj. J. 14, 631–638 (1997). doi:10.1023/A:1018544711767

    Article  CAS  PubMed  Google Scholar 

  10. Zimmermann-Belsing, T., Feldt-Rasmussen, U., From, G., Perrild, H., Bog-Hansen, T.C.: Long-term pathologic changes of α1-acid glycoprotein (orosomucoid) glycoforms in autoimmune thyroid disease. Autoimmunity 35, 441–447 (2002). doi:10.1080/0891693021000038721

    Article  CAS  PubMed  Google Scholar 

  11. Fournier, T., Medjoubi, N.N., Porquet, D.: Alpha-1-acid glycoprotein. Biochim. Biophys. Acta 1482, 157–171 (2000)

    CAS  PubMed  Google Scholar 

  12. Naitosh, A., Aoyagi, Y., Asakura, H.: Highly enhanced fucosylation of serum glycoproteins in patients with hepatocellular carcinoma. J. Gastroenterol. Hepatol. 14, 436–445 (1999). doi:10.1046/j.1440-1746.1999.01882.x

    Article  Google Scholar 

  13. Hada, T., Kondo, M., Yasukawa, K., Amuro, Y., Higashino, K.: Enzyme-linked immunosorbent assay (ELISA) for Aleuria aurantia lectin-reactive serum cholinesterase to differentiate liver cirrhosis and chronic hepatitis. Clin. Chim. Acta 243, 1–9 (1995). doi:10.1016/0009-8981(95)06146-0

    Article  PubMed  Google Scholar 

  14. Ryden, I., Lundblad, A., Pahlsson, P.: Lectin ELISA for analysis of α1-acid glycoprotein fucosylation in the acute phase response. Clin. Chem. 45, 2010–2012 (1999)

    CAS  PubMed  Google Scholar 

  15. Lowry, O.H., Rosbrough, N.J., Farr, A.L., Randall, R.J.: Protein measurement with the folin reagent. J. Biol. Chem. 193, 265–275 (1951)

    CAS  PubMed  Google Scholar 

  16. Gorg, A., Postal, W., Gunther, S.: Two-dimensional electrophoresis. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 9, 531–546 (1988). doi:10.1002/elps.1150090913

    Article  CAS  PubMed  Google Scholar 

  17. Towbin, H., Stehelin, T., Gordon, J.: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl Acad. Sci. USA 76, 4350 (1979). doi:10.1073/pnas.76.9.4350

    Article  CAS  PubMed  Google Scholar 

  18. Chaven, M.M., Kawle, P.D., Mehta, N.G.: Increased sialylation and defucosylation of plasma proteins are early events in the acute phase response. Glycobiology 15, 838–848 (2005). doi:10.1093/glycob/cwi067

    Article  Google Scholar 

  19. Das, H.R., Jayaraman, V., Bhattacharya, I.: Carbohydrate analysis of bradyrhizobial (NC92) lipopolysaccharides by high performance-anion exchange chromatography with pulsed amperometric detection. Biosci. Rep. 19, 219–225 (1999). doi:10.1023/A:1020281921029

    Article  CAS  PubMed  Google Scholar 

  20. Hashimoto, S., Asao, T., Takahashi, J., Yagihashi, Y., Nishimura, T., Saniabadi, A.R., Poland, D.C.W., van Dijk, W., Kuwano, H., Kochibe, N., Yazawa, S.: α1-Acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis. Cancer 101, 2825–2836 (2004). doi:10.1002/cncr.20713

    Article  CAS  PubMed  Google Scholar 

  21. Kratz, E., Poland, D.C.W., van Dijk, W., Katnik-Prastowska, I.: Alterations of branching and differential expression of sialic acid on alpha-1-acid glycoprotein in human seminal plasma. Clin. Chim. Acta 331, 87–95 (2003). doi:10.1016/S0009-8981(03)00084-6

    Article  CAS  PubMed  Google Scholar 

  22. Mooney, P., Hayes, P., Smith, K.: The putative use of α1-acid glycoprotein as a non-invasive marker of fibrosis. Biomed. Chromatogr. 20, 1351–1358 (2006). doi:10.1002/bmc.704

    Article  CAS  PubMed  Google Scholar 

  23. Liedberg, B., Lundstrom, I., Stenberg, E.: Principles of biosensing with an extended coupling matrix and surface plasmon resonance. Sens. Actuators B Chem. 11, 63–72 (1993)

    Article  Google Scholar 

  24. Turner, G.A.: N-glycosylation of serum proteins in disease and its investigation using lectins. Clin. Chim. Acta 208, 149–171 (1992). doi:10.1016/0009-8981(92)90073-Y

    Article  CAS  PubMed  Google Scholar 

  25. Kim, K.A., Lee, E.Y., Kang, J.H., Lee, H.G., Kim, J.W., Kwon, D.H., Jang, Y.J., Yeom, Y.I., Chung, T.W., Kim, Y.D., Yoon, D.Y., Song, E.Y.: Diagnostic accuracy of serum asialo-α1-acid glycoprotein concentration for the differential diagnosis of liver cirrhosis and hepatocellular carcinoma. Clin. Chim. Acta 369, 46–51 (2006). doi:10.1016/j.cca.2006.01.002

    Article  CAS  PubMed  Google Scholar 

  26. Gravel, P., Walzer, C., Aubry, C., Balant, L.P., Yersin, B., Hochstrasser, D.F., Guimon, J.: New alterations of serum glycoproteins in alcoholic and cirrhotic patients revealed by high resolution two-dimensional gel electrophoresis. Biochem. Biophys. Res. Commun. 220, 78–85 (1996). doi:10.1006/bbrc.1996.0360

    Article  CAS  PubMed  Google Scholar 

  27. Biou, D., Wieruszeski, J.M., Konan, D., Fournet, B., Durand, G.: Hyperfucosylation of α1-acid glycoprotein during cirrhosis. Prog. Clin. Biol. Res. 300, 215–218 (1989)

    CAS  PubMed  Google Scholar 

  28. Thompson, S., Matta, K.L., Turner, G.A.: Changes in fucose metabolism associated with heavy drinking and smoking: a preliminary report. Clin. Chim. Acta 201, 59–64 (1991). doi:10.1016/0009-8981(91)90024-7

    Article  CAS  PubMed  Google Scholar 

  29. Mann, A.C., Record, C.O., Self, C.H., Turner, G.A.: Monosaccharide composition of haptoglobin in liver diseases and alcohol abuse: large changes in glycosylation associated with alcoholic liver disease. Clin. Chim. Acta 227, 69–78 (1994). doi:10.1016/0009-8981(94)90136-8

    Article  CAS  PubMed  Google Scholar 

  30. Kondo, M., Hada, T., Fukui, K., Iwasaki, A., Higashino, K., Yasukawa, K.: Enzyme-linked immunosorbent assay (ELISA) for Aleuria aurantia lectin-reactive serum cholinesterase to differentiate liver cirrhosis and chronic hepatitis. Clin. Chim. Acta 243, 1–9 (1995). doi:10.1016/0009-8981(95)06146-0

    Article  CAS  PubMed  Google Scholar 

  31. Aoyagi, Y., Saitoh, A., Suzuki, Y., Igarashi, K., Oguro, M., Yokota, T.: Fucosylation index of α-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis. Hepatology 17, 50–52 (1993)

    Article  CAS  PubMed  Google Scholar 

  32. Yamashita, K., Koide, N., Endo, T., Iwaki, Y., Kobata, A.: Altered glycosylation of serum transferrin of patients with hepatocellular carcinoma. J. Biol. Chem. 264, 2415–2423 (1989)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors sincerely thank to Dr. A. K. Santra, Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata for providing HBV-CH patients sera and Prof. Y. K Chawla, Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh for providing HBV liver cirrhosis (HBV-LC) patients sera. The authors accord high appreciation to Dr. Sharmistha De, Department of Biophysics, All India Institute of Medical Sciences, New Delhi for conducting SPR analysis. Urmimala Chatterjee acknowledges the Department of Biotechnology, Government of India, New Delhi for fellowship. This study was financially supported by a research grant (BT/PR4462/BRB/10/350/2003) of DBT, New Delhi to B.P.C.

Author information

Author notes

  1. Urmimala Chatterjee

    Present address: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agriculture Science, Uppsala, Sweden

Authors and Affiliations

  1. Department of Natural Science, Humanities and Management, West Bengal University of Technology, BF-142, Salt Lake, Sector-1, Kolkata, 700 064, India

    Gautam Mondal, Urmimala Chatterjee & Bishnu P. Chatterjee

  2. Institute of Genomics & Integrative Biology, Mall Road, Delhi, 110007, India

    Hasi R. Das

Authors
  1. Gautam Mondal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Urmimala Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hasi R. Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bishnu P. Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bishnu P. Chatterjee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mondal, G., Chatterjee, U., Das, H.R. et al. Enhanced expression of α1-acid glycoprotein and fucosylation in hepatitis B patients provides an insight into pathogenesis. Glycoconj J 26, 1225–1234 (2009). https://doi.org/10.1007/s10719-009-9241-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-009-9241-1

Keywords

Search

Navigation