Analytical and Bioanalytical Chemistry

, Volume 399, Issue 10, pp 3529–3539 | Cite as

Glycation and oxidation of histones H2B and H1: in vitro study and characterization by mass spectrometry

  • Sofia Guedes
  • Rui Vitorino
  • Maria R. M. Domingues
  • Francisco Amado
  • Pedro Domingues
Original Paper

Abstract

Among the post-translational modifications, oxidation and glycation are of special interest, especially in diseases such as diabetes, and in aging. The synergistic interaction between glycation and oxidation, also known as “glycoxidation” is highly relevant due to its involvement in the production of deleterious changes at the molecular level. Non-enzymatic damage to nuclear proteins has potentially severe consequences for the maintenance of genomic integrity [54]. In this report, we study glycated histones and its in vitro oxidation. Data concerning the modifications that occurred in the histones were obtained by analysis of enzymatic digests (Glu-C and Arg-C) of unmodified and glycated histones, obtained before and after oxidation. Analysis was then performed using a MALDI-MS/MS-based approach combined with nano liquid chromatography. This approach allowed us to identify histone H2B and H1 specific-sites of oxidation and to distinguish the most affected residues for each histone. The results showed the occurrence of a cumulative effect of oxidative damage in the glycated histones when subjected to in vitro oxidation, suggesting that structural changes caused by glycation induces histones to a pro-oxidant state. Comparing the data of oxidized glycated histones with data from unmodified oxidized histones, using the same model of oxidation, the results clearly show that these oxidative modifications occur earlier and more extensively in glycated histones. Furthermore, the results pointed to an increased oxidative damage in the vicinity of the glycated residues.

Keywords

Histones Glycation Protein oxidation Mass spectrometry 

Supplementary material

216_2011_4679_MOESM1_ESM.pdf (444 kb)
ESM 1(PDF 443 kb)

References

  1. 1.
    Han KK, Martinage A (1992) Post-translational chemical modification(s) of proteins. Int J Biochem 24:19–28CrossRefGoogle Scholar
  2. 2.
    Stadtman ER (1990) Covalent modification reactions are marking steps in protein turnover. Biochemistry 29:6323–6331CrossRefGoogle Scholar
  3. 3.
    Bucala R, Cerami A (1992) Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 23:1–34CrossRefGoogle Scholar
  4. 4.
    Clarke S (2003) Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair. Ageing Res Rev 2:263–285CrossRefGoogle Scholar
  5. 5.
    Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412CrossRefGoogle Scholar
  6. 6.
    Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9CrossRefGoogle Scholar
  7. 7.
    Piconi L, Quagliaro L, Ceriello A (2003) Oxidative stress in diabetes. Clin Chem Lab Med 41:1144–1149CrossRefGoogle Scholar
  8. 8.
    Pamplona R, Dalfo E, Ayala V, Bellmunt MJ, Prat J, Ferrer I, Portero-Otin M (2005) Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J Biol Chem 280:21522–21530CrossRefGoogle Scholar
  9. 9.
    Smith MA, Richey PL, Taneda S, Kutty RK, Sayre LM, Monnier VM, Perry G (1994) Advanced Maillard reaction end products, free radicals, and protein oxidation in Alzheimer’s disease. Ann N Y Acad Sci 738:447–454CrossRefGoogle Scholar
  10. 10.
    Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci U S A 91:4766–4770CrossRefGoogle Scholar
  11. 11.
    Cho SJ, Roman G, Yeboah F, Konishi Y (2007) The road to advanced glycation end products: a mechanistic perspective. Curr Med Chem 14:1653–1671CrossRefGoogle Scholar
  12. 12.
    Lapolla A, Fedele D, Martano L, Arico NC, Garbeglio M, Traldi P, Seraglia R, Favretto D (2001) Advanced glycation end products: a highly complex set of biologically relevant compounds detected by mass spectrometry. J Mass Spectrom 36:370–378CrossRefGoogle Scholar
  13. 13.
    Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56:1–21CrossRefGoogle Scholar
  14. 14.
    Pilková L, Pokorný J, Davídek J (1990) Browning reactions of Heyns rearrangement products. Food/Nahrung 34:759–764CrossRefGoogle Scholar
  15. 15.
    Amadori M (1925) Atii real accad naz Lincei 2:337–345Google Scholar
  16. 16.
    Morgan PE, Dean RT, Davies MJ (2002) Inactivation of cellular enzymes by carbonyls and protein-bound glycation/glycoxidation products. Arch Biochem Biophys 403:259–269CrossRefGoogle Scholar
  17. 17.
    Wolff SP, Dean RT (1987) Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes. Biochem J 245:243–250Google Scholar
  18. 18.
    Sen S, Kar M, Roy A, Chakraborti AS (2005) Effect of nonenzymatic glycation on functional and structural properties of hemoglobin. Biophys Chem 113:289–298CrossRefGoogle Scholar
  19. 19.
    Zeng J, Dunlop RA, Rodgers KJ, Davies MJ (2006) Evidence for inactivation of cysteine proteases by reactive carbonyls via glycation of active site thiols. Biochem J 398:197–206CrossRefGoogle Scholar
  20. 20.
    Yamada H, Sasaki T, Niwa S, Oishi T, Murata M, Kawakami T, Aimoto S (2004) Intact glycation end products containing carboxymethyl-lysine and glyoxal lysine dimer obtained from synthetic collagen model peptide. Bioorg Med Chem Lett 14:5677–5680CrossRefGoogle Scholar
  21. 21.
    Baynes JW (2002) The Maillard hypothesis on aging: time to focus on DNA. Ann N Y Acad Sci 959:360–367CrossRefGoogle Scholar
  22. 22.
    Breitling-Utzmann CM, Unger A, Friedl DA, Lederer MO (2001) Identification and quantification of phosphatidylethanolamine-derived glucosylamines and aminoketoses from human erythrocytes–influence of glycation products on lipid peroxidation. Arch Biochem Biophys 391:245–254CrossRefGoogle Scholar
  23. 23.
    Ferretti G, Bacchetti T, Marchionni C, Dousset N (2004) Effect of non-enzymatic glycation on aluminium-induced lipid peroxidation of human high density lipoproteins (HDL). Nutr Metab Cardiovasc Dis 14:358–365CrossRefGoogle Scholar
  24. 24.
    Roy A, Sen S, Chakraborti AS (2004) In vitro nonenzymatic glycation enhances the role of myoglobin as a source of oxidative stress. Free Radic Res 38:139–146CrossRefGoogle Scholar
  25. 25.
    Wondrak GT, Jacobson EL, Jacobson MK (2002) Photosensitization of DNA damage by glycated proteins. Photochem Photobiol Sci 1:355–363CrossRefGoogle Scholar
  26. 26.
    Talasz H, Wasserer S, Puschendorf B (2002) Nonenzymatic glycation of histones in vitro and in vivo. J Cell Biochem 85:24–34CrossRefGoogle Scholar
  27. 27.
    Gugliucci A (1994) Advanced glycation of rat liver histone octamers: an in vitro study. Biochem Biophys Res Commun 203:588–593CrossRefGoogle Scholar
  28. 28.
    Gugliucci A, Bendayan M (1995) Histones from diabetic rats contain increased levels of advanced glycation end products. Biochem Biophys Res Commun 212:56–62CrossRefGoogle Scholar
  29. 29.
    Cervantes-Laurean D, Jacobson EL, Jacobson MK (1996) Glycation and glycoxidation of histones by ADP-ribose. J Biol Chem 271:10461–10469CrossRefGoogle Scholar
  30. 30.
    Luxford C, Morin B, Dean RT, Davies MJ (1999) Histone H1- and other protein- and amino acid-hydroperoxides can give rise to free radicals which oxidize DNA. Biochem J 344(Pt 1):125–134CrossRefGoogle Scholar
  31. 31.
    Bonenfant D, Coulot M, Towbin H, Schindler P, van Oostrum J (2006) Characterization of histone H2A and H2B variants and their post-translational modifications by mass spectrometry. Mol Cell Proteomics 5:541–552Google Scholar
  32. 32.
    Bonenfant D, Towbin H, Coulot M, Schindler P, Mueller DR, van Oostrum J (2007) Analysis of dynamic changes in post-translational modifications of human histones during cell cycle by mass spectrometry. Mol Cell Proteomics 6:1917–1932CrossRefGoogle Scholar
  33. 33.
    Cocklin RR, Wang M (2003) Identification of methylation and acetylation sites on mouse histone H3 using matrix-assisted laser desorption/ionization time-of-flight and nanoelectrospray ionization tandem mass spectrometry. J Protein Chem 22:327–334CrossRefGoogle Scholar
  34. 34.
    Freitas MA, Sklenar AR, Parthun MR (2004) Application of mass spectrometry to the identification and quantification of histone post-translational modifications. J Cell Biochem 92:691–700CrossRefGoogle Scholar
  35. 35.
    Garcia BA, Busby SA, Barber CM, Shabanowitz J, Allis CD, Hunt DF (2004) Characterization of phosphorylation sites on histone H1 isoforms by tandem mass spectrometry. J Proteome Res 3:1219–1227CrossRefGoogle Scholar
  36. 36.
    Su X, Jacob NK, Amunugama R, Lucas DM, Knapp AR, Ren C, Davis ME, Marcucci G, Parthun MR, Byrd JC, Fishel R, Freitas MA (2007) Liquid chromatography mass spectrometry profiling of histones. J Chromatogr B Analyt Technol Biomed Life Sci 850:440–454CrossRefGoogle Scholar
  37. 37.
    Zhang K, Tang H, Huang L, Blankenship JW, Jones PR, Xiang F, Yau PM, Burlingame AL (2002) Identification of acetylation and methylation sites of histone H3 from chicken erythrocytes by high-accuracy matrix-assisted laser desorption ionization-time-of-flight, matrix-assisted laser desorption ionization-postsource decay, and nanoelectrospray ionization tandem mass spectrometry. Anal Biochem 306:259–269CrossRefGoogle Scholar
  38. 38.
    Picotti P, Aebersold R, Domon B (2007) The implications of proteolytic background for shotgun proteomics. Mol Cell Proteomics 6:1589–1598CrossRefGoogle Scholar
  39. 39.
    Creasy DM, Cottrell JS (2004) Unimod: protein modifications for mass spectrometry. Proteomics 4:1534–1536CrossRefGoogle Scholar
  40. 40.
    Frolov A, Hoffmann P, Hoffmann R (2006) Fragmentation behavior of glycated peptides derived from d-glucose, d-fructose and d-ribose in tandem mass spectrometry. J Mass Spectrom 41:1459–1469CrossRefGoogle Scholar
  41. 41.
    Frolov A, Hoffmann R (2010) Identification and relative quantification of specific glycation sites in human serum albumin. Anal Bioanal Chem 397:2349–2356CrossRefGoogle Scholar
  42. 42.
    Montgomery H, Tanaka K, Belgacem O (2010) Glycation pattern of peptides condensed with maltose, lactose and glucose determined by ultraviolet matrix-assisted laser desorption/ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 24:841–848CrossRefGoogle Scholar
  43. 43.
    Liebich HM, Gesele E, Wirth C, Woll J, Jobst K, Lakatos A (1993) Non-enzymatic glycation of histones. Biol Mass Spectrom 22:121–123CrossRefGoogle Scholar
  44. 44.
    Guedes S, Vitorino R, Domingues R, Amado F, Domingues P (2009) Oxidation of bovine serum albumin: identification of oxidation products and structural modifications. Rapid Commun Mass Spectrom 23:2307–2315CrossRefGoogle Scholar
  45. 45.
    Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272:20313–20316CrossRefGoogle Scholar
  46. 46.
    Requena JR, Chao CC, Levine RL, Stadtman ER (2001) Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proc Natl Acad Sci U S A 98:69–74CrossRefGoogle Scholar
  47. 47.
    Stadtman ER, Levine RL (2003) Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids 25:207–218CrossRefGoogle Scholar
  48. 48.
    Schoneich C, Sharov VS (2006) Mass spectrometry of protein modifications by reactive oxygen and nitrogen species. Free Radic Biol Med 41:1507–1520CrossRefGoogle Scholar
  49. 49.
    Guan JQ, Chance MR (2005) Structural proteomics of macromolecular assemblies using oxidative footprinting and mass spectrometry. Trends Biochem Sci 30:583–592CrossRefGoogle Scholar
  50. 50.
    Stadtman ER, Berlett BS (1991) Fenton chemistry. Amino acid oxidation. J Biol Chem 266:17201–17211Google Scholar
  51. 51.
    Guedes S, Vitorino R, Domingues MR, Amado F, Domingues P (2010) Oxidative modifications in glycated insulin. Anal Bioanal Chem 397:1985–1995CrossRefGoogle Scholar
  52. 52.
    Chetyrkin SV, Mathis ME, Ham AJ, Hachey DL, Hudson BG, Voziyan PA (2008) Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine. Free Radic Biol Med 44:1276–1285CrossRefGoogle Scholar
  53. 53.
    Yim MB, Kang SO, Chock PB (2000) Enzyme-like activity of glycated cross-linked proteins in free radical generation. Ann N Y Acad Sci 899:168–181CrossRefGoogle Scholar
  54. 54.
    Wondrak GT, Cervantes-Laueant, Jacobson EL, Jacobson MK (2000) Histone carbonylation in vivo and in vitro. Biochem. J. 351:769–777Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sofia Guedes
    • 1
  • Rui Vitorino
    • 1
  • Maria R. M. Domingues
    • 1
  • Francisco Amado
    • 1
  • Pedro Domingues
    • 1
  1. 1.Department of ChemistryUniversity of AveiroAveiroPortugal

Personalised recommendations