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Structural Heterogeneity of Glycoform of Alpha-1 Acid Glycoprotein in Alcoholic Cirrhosis Patients

  • Goutam Mandal
  • Hirokazu Yagi
  • Koichi Kato
  • Bishnu Pada ChatterjeeEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 842)

Abstract

Altered glycosylation of serum proteins has been reported in different pathologic conditions. Changes in glycosylation of serum proteins in disease state have been extensively used for the development of noninvasive sensitive clinical tests for diagnostic purposes. The aim of the present research was to monitor the changes of glycoform of serum alpha1-acid glycoprotein (AGP) in alcoholic liver cirrhosis (ALC) patients which could be predicted as serological marker for diagnosis. AGP was isolated from the albumin depleted pooled sera of ALC patients as well as controls by monoclonal anti-AGP affinity column. The altered glycoforms of AGP was determined by HPLC mapping followed by mass spectrometry and GALAXY database search. N-glycans released from AGP by hydrazinolysis were labeled with 2-aminopyridine and separated by three successive HPLC columns, viz., DEAE, ODS and amide silica. Significant decrease of sialylation level was observed by HPLC in ALC patients group with respect to controls. The binding of SNA with AGP was found to be less in patients group than control by ELISA and lectin blotting using Sambucus nigra agglutinin (SNA). This variation of N-linked glycoforms and decreased level of sialic acid in AGP could be valuable for the diagnosis of ALC besides clinical examination and routine laboratory investigation that could be helpful for treatment strategy.

Keywords

Alpha-1-acid glycoprotein Glycosylation Alcoholic liver cirrhosis HPLC Sialic acid 

List of Abbreviations

2-PA

2-Aminopyridine

AAT

Alpha-1 antitrypsin

ACT

Alpha-1 antichymotrypsin

AGP

Alpha1-acid glycoprotein

ALC

Alcoholic liver cirrhosis

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

CDT

Carbohydrate-deficient transferrin

DEAE

Diethylaminoethyl

GU

Glucose unit

Hp

Haptoglobin

ODS

Octadecyl silica

SNA

Sambucus nigra agglutinin

Tf

Transferrin

Notes

Acknowledgements

The authors sincerely thank Prof. Y. K. Chawla, Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India for providing patients’ sera. This study was supported in part by Grants from IMS for IMS visiting Professor from abroad and the Japan Society for the Promotion of Science (JSPS) Invitational Training Program for Advanced Japanese Research Institutes. BPC and GM gratefully acknowledge the research grant (52/22/2008-BMS) provided by the Indian Council of Medical Research, New Delhi.

References

  1. Arndt T (2001) Carbohydrate-deficient transferrin as a marker of chronic alcohol abuse: a critical review of preanalysis, analysis, and interpretation. Clin Chem 47:13–27CrossRefGoogle Scholar
  2. Baenziger JU (1984) The oligosaccharides of plasma glycoproteins: synthesis, structure, and function. In: Putnam FW (ed) The plasma proteins, vol 4, 2nd edn. Academic, New York, p 271CrossRefGoogle Scholar
  3. Biou D, Konan D, Feger J (1987) Alterations in the carbohydrate moiety of alpha-1-acid glycoprotein purified from human cirrhotic ascitic fluid. Biochim Biophys Acta 913:308–312CrossRefGoogle Scholar
  4. Biou D, Chanton P, Konan D et al (1989) Microheterogeneity of the carbohydrate moiety of human alpha 1-acid glycoprotein in two benign liver diseases: alcoholic cirrhosis and acute hepatitis. Clin Chim Acta 186:59–66CrossRefGoogle Scholar
  5. Block TM, Comunale MA, Lowman M et al (2005) Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. Proc Natl Acad Sci U S A 102:779–785CrossRefGoogle Scholar
  6. Blomme B, Van Steenkiste C, Callewaert N et al (2009) Alteration of protein glycosylation in liver diseases. J Hepatol 50:592–603CrossRefGoogle Scholar
  7. Brinkman-van der Linden EC, van Ommen EC, van Dijk W (1996) Glycosylation of α-1 glycoprotein in septic shock: changes in degree of branching and in expression of sialyl Lewis(x) groups. Glycoconj J 13:27–31CrossRefGoogle Scholar
  8. Charlwood J, Bryant D, Skehel JM et al (2001) Analysis of N-linked oligosaccharides: progress towards the characterisation of glycoprotein-linked carbohydrates. Biomol Eng 18:229–240CrossRefGoogle Scholar
  9. Comunale MA, Lowman M, Long RE et al (2006) Proteomic analysis of serum associated fucosylated glycoproteins in the development of primary hepatocellular carcinoma. J Proteome Res 6:308–315CrossRefGoogle Scholar
  10. Comunale MA, Rodemich-Betesh L, Hafner J et al (2010) Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma. PLoS One 5:e12419CrossRefGoogle Scholar
  11. Debruyne V, Montreuil J, Spik G (1984) Crossed immunoaffinity electrophoresis of human transferring in normal and cirrhotic sera. In: Peeters H (ed) Protides Biol. Fluids Proc. Colloq., vol 31. Pergamon, Oxford, pp 63–68Google Scholar
  12. Hachulla E, Laine A, Hedouin V et al (1992) Variations in the glycoforms of serum alpha 1-antichymotrypsin in liver diseases and after liver transplantation. Clin Sci 82:439–446CrossRefGoogle Scholar
  13. Hada T, Kondo M, Yasukawa K et al (1999) Discrimination of liver cirrhosis from chronic hepatitis by measuring the ratio of Aleuria aurantia lectin-reactive serum cholinesterase to immunoreactive protein. Clin Chim Acta 281:37–46CrossRefGoogle Scholar
  14. Jezequel M, Seta NS, Corbic MM et al (1988) Modifications of concanavalin A patterns of alpha 1-acid glycoprotein and alpha 2-HS glycoprotein in alcoholic liver disease. Clin Chim Acta 176:49–57CrossRefGoogle Scholar
  15. Kondo M, Hada T, Fukui K et al (1995) Enzyme-linked immunosorbent assay (ELISA) for Aleuria aurantia lectin-reactive serum cholinesterase to differentiate liver cirrhosis and chronic hepatitis. Clin Chim Acta 243:1–9CrossRefGoogle Scholar
  16. Mann AC, Record CO, Self CH et al (1994) Monosaccharide composition of haptoglobin in liver diseases and alcohol abuse: large changes in glycosylation associated with alcoholic liver disease. Clin Chim Acta 227:69–78CrossRefGoogle Scholar
  17. Maryvonne J, Nathalie S, Corbic M et al (1988) Modifications of concanavalin A patterns of alpha 1-acid glycoprotein and alpha 2-HS glycoprotein in alcoholic liver disease. Clin Chim Acta 176:49–57CrossRefGoogle Scholar
  18. Mondal G, Chatterjee U, Das HR et al (2009) Enhanced expression of alpha1-acid glycoprotein and fucosylation in hepatitis B patients provides an insight into pathogenesis. Glycoconj J 26:1225–1234CrossRefGoogle Scholar
  19. Mondal G, Chatterjee U, Chawla YK et al (2011) Alterations of glycan branching and differential expression of sialic acid on alpha fetoprotein among hepatitis patients. Glycoconj J 28:1–9CrossRefGoogle Scholar
  20. Nicollet I, Lebreton JP, Fontaine M et al (1981) Evidence for alpha-1-acid glycoprotein populations of different pI values after concanavalin A affinity chromatography. Study of their evolution during inflammation in man. Biochim Biophys Acta 668:235–245CrossRefGoogle Scholar
  21. Patricia G, Claude W, Christiane A et al (1996) New alterations of serum glycoproteins in alcoholic and cirrhotic patients revealed by high resolution two-dimensional gel electrophoresis. Biochem Biophy Res Commun 220:78–85CrossRefGoogle Scholar
  22. Ryden I, Skude G, Lundblad A et al (1997) Glycosylation of alpha1-acid glycoprotein in inflammatory disease: analysis by high-pH anion-exchange chromatography and concanavalin A crossed affinity immunoelectrophoresis. Glycoconj J 14:481–488CrossRefGoogle Scholar
  23. Ryden I, Lundblad A, Pahlsson P (1999) Lectin ELISA for analysis of alpha (1)-acid glycoprotein fucosylation in the acute phase response. Clin Chem 45:2010–2012CrossRefGoogle Scholar
  24. Saroha A, Kumar S, Chatterjee BP et al (2012) Jacalin bound plasma O-glycoproteome and reduced sialylation of alpha 2-HS glycoprotein (A2HSG) in rheumatoid arthritis patients. PLoS One 2:e46374CrossRefGoogle Scholar
  25. Serbource-Goguel Seta M, Bordas M, Davy J et al (1984) Evaluation of the degree of desialylation of serum C1-inactivator and haemopexin. Clin Chim Acta 143:235–241CrossRefGoogle Scholar
  26. Serbource-Goguel Seta N, Durand G, Corbic M et al (1986) Alterations in relative proportions of microheterogenous forms of human alpha 1-acid glycoprotein in liver disease. J Hepatol 2:245–252CrossRefGoogle Scholar
  27. Serbource-Goguel N, Corbtc M, Erlinger S et al (1983) Measurement of serum alpha 1-acid glycoprotein and alpha 1-antitrypsin desialylation in liver disease. Hepatology 3:356–390CrossRefGoogle Scholar
  28. Stibler H, Borg S (1981) Evidence of reduced sialic acid content in serum transferrin in male alcoholics. Alcohol Clin Exp Res 5:545–549CrossRefGoogle Scholar
  29. Stibler H, Borg S (1986) Carbohydrate composition of serum transferrin in alcoholic patients. Alcohol Clin Exp Res 10:61–64CrossRefGoogle Scholar
  30. Takahashi N, Kato K (2003) GALAXY (Glycoanalysis by the three axes of MS and chromatography): a web application that assists structural analyses of N-glycans. Trends Glycosci Glycotechnol 15:235–251CrossRefGoogle Scholar
  31. Thompson S, Matta KL, Turner G (1991) Changes in fucose metabolism associated with heavy drinking and smoking: a preliminary report. Clin Chim Acta 201:59–64CrossRefGoogle Scholar
  32. Tsutsumi M, Wang JS, Takada A (1994) Microheterogeneity of serum glycoproteins in alcoholics: is desialo-transferrin the marker of chronic alcohol drinking or alcoholic liver injury? Alcohol Clin Exp Res 18:392–397CrossRefGoogle Scholar
  33. Turner GA (1992) N-glycosylation of serum proteins in disease and its investigation using lectins. Clin Chim Acta 208:149–171CrossRefGoogle Scholar
  34. Yagi H, Takahashi N, Yamaguchi Y, Kato K et al (2005) Development of structural analysis of sulfated N-glycans by multidimensional high performance liquid chromatography mapping methods. Glycobiology 15:1051–1060CrossRefGoogle Scholar
  35. Yagi H, Yamamoto M, Yu S et al (2010) N-Glycosylation profiling of turtle egg yolk: expression of galabiose structure. Carbohydr Res 345:442–448CrossRefGoogle Scholar
  36. Yamamoto S, Hase S, Fukuda S et al (1989) Studies on the sugar chains of interferon-γ from human peripheral-blood lymphocytes. J Biochem 105:547–555CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Goutam Mandal
    • 1
  • Hirokazu Yagi
    • 2
  • Koichi Kato
    • 2
    • 3
  • Bishnu Pada Chatterjee
    • 1
    Email author
  1. 1.Department of Natural SciencesWest Bengal University of TechnologySalt LakeIndia
  2. 2.Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
  3. 3.Institute for Molecular Science and Okazaki Institute for Integrative BioscienceNational Institutes of Natural Sciences, Okazaki Institute for Integrative BiosciencesOkazakiJapan

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