Molecular and Cellular Biochemistry

, Volume 357, Issue 1–2, pp 323–330 | Cite as

Comparison of glycation of glutathione S-transferase by methylglyoxal, glucose or fructose

  • Iva Boušová
  • Zuzana Průchová
  • Lucie Trnková
  • Jaroslav Dršata
Article

Abstract

Glycation is a process closely related to the aging and pathogenesis of diabetic complications. In this process, reactive α-dicarbonyl compounds (e.g., methylglyoxal) cause protein modification accompanied with potential loss of their biological activity and persistence of damaged molecules in tissues. We suppose that glutathione S-transferases (GSTs), a group of cytosolic biotransformation enzymes, may be modified by glycation in vivo, which would provide a rationale of its use as a model protein for studying glycation reactions. Glycation of GST by methylglyoxal, fructose, and glucose in vitro was studied. The course of protein glycation was evaluated using the following criteria: enzyme activity, formation of advanced glycation end-products using fluorescence and western blotting, amine content, protein conformation, cross linking and aggregation, and changes in molecular charge of GST. The ongoing glycation by methylglyoxal 2 mM resulted in pronounced decrease in the GST activity. It also led to the loss of 14 primary amino groups, which was accompanied by changes in protein mobility during native polyacrylamide gel electrophoresis. Formation of cross links with molecular weight of 75 kDa was observed. Obtained results can contribute to understanding of changes, which proceed in metabolism of xenobiotics during diabetes mellitus and ageing.

Keywords

Advanced glycation end-products Glutathione S-transferase Methylglyoxal Protein glycation Protein conformation 

References

  1. 1.
    Uetrecht JP, Trager W (2007) Drug metabolism: chemical and enzymatic aspects. Informa Healthcare, New YorkGoogle Scholar
  2. 2.
    van Bladeren PJ (2000) Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 129:61–76PubMedCrossRefGoogle Scholar
  3. 3.
    Dourado DF, Fernandes PA, Ramos MJ (2008) Mammalian cytosolic glutathione transferases. Curr Protein Pept Sci 9:325–337PubMedCrossRefGoogle Scholar
  4. 4.
    Nebert DW, Vasiliou V (2004) Analysis of the glutathione S-transferase (GST) gene family. Hum Genomics 1:460–464PubMedGoogle Scholar
  5. 5.
    Sheehan D, Meade G, Foley VM, Dowd CA (2001) Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 360:1–16PubMedCrossRefGoogle Scholar
  6. 6.
    Mannervik B, Danielson UH (1988) Glutathione transferases—structure and catalytic activity. Crit Rev Biochem 23:283–337CrossRefGoogle Scholar
  7. 7.
    Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, New YorkGoogle Scholar
  8. 8.
    Hunt JV, Dean RT, Wolff SP (1988) Hydroxyl radical production and autooxidative glycosylation. Glucose autoxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem J 256:205–212PubMedGoogle Scholar
  9. 9.
    Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56:1–22PubMedCrossRefGoogle Scholar
  10. 10.
    Schalkwijk CG, Stehouwer CD, van Hinsbergh VW (2004) Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab Res Rev 20:369–382PubMedCrossRefGoogle Scholar
  11. 11.
    Matsumoto K, Sano H, Nagai R, Suzuki H, Kodama T, Yoshida M, Ueda S, Smedsrød B, Horiuchi S (2000) Endocytic uptake of advanced glycation end products by mouse liver sinusoidal endothelial cells is mediated by a scavenger receptor distinct from the macrophage scavenger receptor class A. Biochem J 352:233–240PubMedCrossRefGoogle Scholar
  12. 12.
    Ohgami N, Nagai R, Miyazaki A, Ikemoto M, Arai H, Horiuchi S, Nakayama H (2001) Scavenger receptor class B type I-mediated reverse cholesterol transport is inhibited by advanced glycation end products. J Biol Chem 276:13348–13355PubMedCrossRefGoogle Scholar
  13. 13.
    Raza H, Ahmed I, John A (2004) Tissue specific expression and immunohistochemical localization of glutathione S-transferase in streptozocin induced diabetic rats: modulation by Momordica charantia (karela) extract. Life Sci 74:1503–1511PubMedCrossRefGoogle Scholar
  14. 14.
    Lapshina EA, Sudnikovich EJ, Maksimchik JZ, Zabrodskaya SV, Zavodnik LB, Kubyshin VL, Nocun M, Kazmierczak P, Dobaczewski M, Watala C, Zavodnik IB (2006) Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment. Life Sci 79:1804–1811PubMedCrossRefGoogle Scholar
  15. 15.
    Thomas H, Schladt L, Knehr M, Oesch F (1989) Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal β-oxidation. Biochem Pharmacol 38:4291–4297PubMedCrossRefGoogle Scholar
  16. 16.
    Saito-Yamanaka N, Yamanaka H, Nagasawa S (1993) Glutathione-related detoxication functions in streptozocin-induced diabetic rats. J Vet Med Sci 55:991–994PubMedCrossRefGoogle Scholar
  17. 17.
    Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139PubMedGoogle Scholar
  18. 18.
    Steinbrecher UP (1987) Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem 262:3603–3608PubMedGoogle Scholar
  19. 19.
    Ornstein L (1964) Disc electrophoresis. I. Background and theory. Ann NY Acad Sci 121:321–349PubMedCrossRefGoogle Scholar
  20. 20.
    Davies BJ (1964) Disc electrophoresis. II. Method and application to human serum proteins. Ann NY Acad Sci 121:404–427CrossRefGoogle Scholar
  21. 21.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  22. 22.
    Towbin H, Stachlin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354PubMedCrossRefGoogle Scholar
  23. 23.
    Lim K, Ho JX, Keeling K, Gilliland GL, Ji X, Rüker F, Carter DC (1994) Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV. Protein Sci 3:2233–2244PubMedCrossRefGoogle Scholar
  24. 24.
    Ji X, Tordova M, O’Donnell R, Parsons JF, Hayden JB, Gilliland GL, Zimniak P (1997) Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase. Biochemistry 36:9690–9702PubMedCrossRefGoogle Scholar
  25. 25.
    Petlevski R, Hadzija M, Slijepcević M, Juretić D, Petrik J (2003) Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytother Res 17:311–314PubMedCrossRefGoogle Scholar
  26. 26.
    Choudhary D, Chandra D, Kale RK (1997) Influence of methylglyoxal on antioxidant enzymes and oxidative damage. Toxicol Lett 93:141–152PubMedCrossRefGoogle Scholar
  27. 27.
    Kang JH (2006) Oxidative modification of human ceruloplasmin by methylglyoxal: an in vitro study. J Biochem Mol Biol 39:335–338PubMedCrossRefGoogle Scholar
  28. 28.
    West IC (2000) Radicals and oxidative stress in diabetes. Diabet Med 17:171–180PubMedCrossRefGoogle Scholar
  29. 29.
    Seidler NW, Kowalewski C (2003) Methylglyoxal-induced glycation affects protein topography. Arch Biochem Biophys 410:149–154PubMedCrossRefGoogle Scholar
  30. 30.
    Thornalley PJ (1996) Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification—a role in pathogenesis and antiproliferative chemotherapy. Gen Pharmacol 27:565–573PubMedGoogle Scholar
  31. 31.
    Seidler NW (2005) Carbonyl-induced enzyme inhibition: mechanism and new perspectives. Curr Enzyme Inhib 1:21–27CrossRefGoogle Scholar
  32. 32.
    Nagai R, Matsumoto K, Ling X, Suzuki H, Araki T, Horiuchi S (2000) Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor. Diabetes 49:1714–1723PubMedCrossRefGoogle Scholar
  33. 33.
    Argirova M, Breipohl W (2002) Comparison between modifications of lens proteins resulted from glycation with methylglyoxal, glyoxal, ascorbic acid, and fructose. J Biochem Mol Toxicol 16:140–145PubMedCrossRefGoogle Scholar
  34. 34.
    Harding JJ (2007) Protein glycation and cataract: a conformational disease. In: Uversky VN, Fink AL (eds) Protein misfolding, aggregation, and conformational diseases. Part B: molecular mechanisms of conformational diseases, 1st edn. Springer Science, New York, pp 499–514CrossRefGoogle Scholar
  35. 35.
    Apostolova LG, Cummings JL (2007) The pathogenesis of Alzheimer’s disease: general overview. In: Uversky VN, Fink AL (eds) Protein misfolding, aggregation, and conformational diseases. Part B: molecular mechanisms of conformational diseases, 1st edn. Springer Science, New York, pp 3–29CrossRefGoogle Scholar
  36. 36.
    Beránek M, Dršata J, Palička V (2001) Inhibitory effect of glycation on catalytic activity of alanine aminotransferase. Mol Cell Biochem 218:35–39PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Iva Boušová
    • 1
  • Zuzana Průchová
    • 1
  • Lucie Trnková
    • 1
    • 2
  • Jaroslav Dršata
    • 1
  1. 1.Department of Biochemical Sciences, Faculty of PharmacyCharles University in PragueHradec KraloveCzech Republic
  2. 2.Department of Chemistry, Faculty of ScienceUniversity of Hradec KrálovéHradec KraloveCzech Republic

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