Advertisement

A Snapshot of the Plant Glycated Proteome

STRUCTURAL, FUNCTIONAL, AND MECHANISTIC ASPECTS*
  • Author Footnotes
    1 These authors made equal contributions to this work.
    Tatiana Bilova
    Footnotes
    1 These authors made equal contributions to this work.
    Affiliations
    Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany

    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany
    Search for articles by this author
  • Author Footnotes
    1 These authors made equal contributions to this work.
    Elena Lukasheva
    Footnotes
    1 These authors made equal contributions to this work.
    Affiliations
    Department of Biochemistry, Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia

    Plant Physiology and Biochemistry, Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
    Search for articles by this author
  • Author Footnotes
    1 These authors made equal contributions to this work.
    Dominic Brauch
    Footnotes
    1 These authors made equal contributions to this work.
    Affiliations
    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany

    Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), D-06466 Stadt Seeland, Germany
    Search for articles by this author
  • Uta Greifenhagen
    Affiliations
    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany
    Search for articles by this author
  • Gagan Paudel
    Affiliations
    Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany

    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany
    Search for articles by this author
  • Elena Tarakhovskaya
    Affiliations
    Plant Physiology and Biochemistry, Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
    Search for articles by this author
  • Nadezhda Frolova
    Affiliations
    Interdisciplinary Center for Crop Plant Research (IZN), Martin Luther University Halle-Wittenberg, D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Juliane Mittasch
    Affiliations
    Interdisciplinary Center for Crop Plant Research (IZN), Martin Luther University Halle-Wittenberg, D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Gerd Ulrich Balcke
    Affiliations
    Departments of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Alain Tissier
    Affiliations
    Departments of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Natalia Osmolovskaya
    Affiliations
    Plant Physiology and Biochemistry, Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
    Search for articles by this author
  • Thomas Vogt
    Affiliations
    Departments of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Ludger A. Wessjohann
    Affiliations
    Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Claudia Birkemeyer
    Affiliations
    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany
    Search for articles by this author
  • Carsten Milkowski
    Affiliations
    Interdisciplinary Center for Crop Plant Research (IZN), Martin Luther University Halle-Wittenberg, D-06120 Halle (Saale), Germany
    Search for articles by this author
  • Andrej Frolov
    Correspondence
    To whom correspondence should be addressed: Leibniz Inst. of Plant Biochemistry, Dept. of Bioorganic Chemistry, Weinberg 3, 06120 Halle/Saale, Germany. Tel.: 49-345-55821370; Fax: 49-345-55821309;
    Affiliations
    Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry (IPB), D-06120 Halle (Saale), Germany

    Faculty of Chemistry and Mineralogy, Universität Leipzig, D-04103 Leipzig, Germany
    Search for articles by this author
  • Author Footnotes
    * This work was supported by Deutsche Forschungsgemeinschaft Grant FR-3117/2-1 (to A. F., G. P., and T. B.), the Ernst-Schering Foundation (to U. G.), the Deutscher Akademischer Austauschdienst DAAD Program “Dmitry Mendeleev” (to E. T. and E. L.), and St. Petersburg University Grant 1.38.233.2014 (to E. L.). The publication of this article was funded by the Open Access fund of the Leibniz Association. The authors declare that they have no conflicts of interest with the contents of this article.
    1 These authors made equal contributions to this work.
Open AccessPublished:January 19, 2016DOI:https://doi.org/10.1074/jbc.M115.678581
      Glycation is the reaction of carbonyl compounds (reducing sugars and α-dicarbonyls) with amino acids, lipids, and proteins, yielding early and advanced glycation end products (AGEs). The AGEs can be formed via degradation of early glycation intermediates (glycoxidation) and by interaction with the products of monosaccharide autoxidation (autoxidative glycosylation). Although formation of these potentially deleterious compounds is well characterized in animal systems and thermally treated foods, only a little information about advanced glycation in plants is available. Thus, the knowledge of the plant AGE patterns and the underlying pathways of their formation are completely missing. To fill this gap, we describe the AGE-modified proteome of Brassica napus and characterize individual sites of advanced glycation by the methods of liquid chromatography-based bottom-up proteomics. The modification patterns were complex but reproducible: 789 AGE-modified peptides in 772 proteins were detected in two independent experiments. In contrast, only 168 polypeptides contained early glycated lysines, which did not resemble the sites of advanced glycation. Similar observations were made with Arabidopsis thaliana. The absence of the early glycated precursors of the AGE-modified protein residues indicated autoxidative glycosylation, but not glycoxidation, as the major pathway of AGE formation. To prove this assumption and to identify the potential modifying agents, we estimated the reactivity and glycative potential of plant-derived sugars using a model peptide approach and liquid chromatography-mass spectrometry-based techniques. Evaluation of these data sets together with the assessed tissue carbohydrate contents revealed dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, ribulose, erythrose, and sucrose as potential precursors of plant AGEs.

      Introduction

      Protein glycation is a ubiquitous post-translational modification (
      • Ulrich P.
      • Cerami A.
      Protein glycation, diabetes, and aging.
      ) formed by the reaction of reducing sugars (aldoses and ketoses) with amino groups of lysyl side chains or N termini, yielding imine intermediates further involved in Amadori (
      • Hodge J.E.
      The Amadori rearrangement.
      ) and Heyns (
      • Heyns K.
      • Noack H.
      Die umsetzung von D-fructose mit L-lysine und L-arginin und deren beziehung zu nichtenzymatischen bräunungsreaktionen.
      ) rearrangement, respectively (Fig. 1). Resulting early glycation products (i.e. keto- and aldamines, respectively) as well as their Schiff base precursors (Namiki pathway) readily undergo further oxidation (glycoxidation) and cross-linking, yielding a heterogeneous group of advanced glycation end products (AGEs)
      The abbreviations used are: AGE, advanced glycation end product; aq., aqueous; Asc, l-ascorbate; BAC, boronic acid affinity chromatography; CEA, Nδ-(carboxyethyl)arginine; CEL, Nϵ-carboxyethyllysine; CML, Nϵ-carboxymethyllysine; Dap, dihydroxyacetone phosphate; DDA, data-dependent acquisition; DHA, dehydroascorbic acid; Ery, d-erythrose; ESI, electrospray ionization; Fmoc, 9-fluorenylmethoxycarbonyl; Fru-P, d-fructose 6-phosphate; f.w., fresh weight; Gal-ol, galactinol dehydrate; Glal-P, d-glyceraldehyde 3-phosphate; Glc-P, d-glucose 6-phosphate; GO, glyoxal; LIT, linear ion trap; Mal, d-maltose; MG-H, methylglyoxal-derived hydroimidazolone, Nδ-(5-methyl-4-oxo-5-hydroimidazolinone-2-yl)-l-ornithine; MGO, methylglyoxal; Orbitrap, orbital trap mass analyzer; ROS, reactive oxygen species; Rubisco, ribulose bisphosphate carboxylase/oxidase; Rul, d-ribulose; Suc, d-sucrose; tR, retention time; QqTOF, quadrupole-time of flight; UPLC, ultrahigh-performance liquid chromatography; XIC, extracted ion chromatogram.
      (
      • Grillo M.A.
      • Colombatto S.
      Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases.
      ). Alternatively, free sugars can be involved in metal-catalyzed autoxidation (
      • Wolff S.P.
      • Dean R.T.
      Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes.
      ), yielding highly reactive α-dicarbonyl compounds glyoxal (GO), methylglyoxal (MGO), and osones (e.g. 3-deoxyglucosone) (
      • Wolff S.P.
      • Dean R.T.
      Aldehydes and dicarbonyls in non-enzymic glycosylation of proteins.
      ). These intermediates can directly react with lysine and arginine side chains of proteins, yielding AGEs (Fig. 1) (
      • Frolov A.
      • Schmidt R.
      • Spiller S.
      • Greifenhagen U.
      • Hoffmann R.
      Formation of arginine-derived advanced glycation end products in peptide-glucose mixtures during boiling.
      ). In mammals, AGEs are markers of aging and atherosclerosis (
      • Luevano-Contreras C.
      • Chapman-Novakofski K.
      Dietary advanced glycation end products and ageing.
      ) and interact with endothelial or macrophage pattern recognition receptors, activating transcription of proinflammatory molecules via nuclear transcription factor κB (NF-κB)-dependent signal transduction pathways (
      • Herold K.
      • Moser B.
      • Chen Y.
      • Zeng S.
      • Yan S.F.
      • Ramasamy R.
      • Emond J.
      • Clynes R.
      • Schmidt A.M.
      Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress.
      ).
      Figure thumbnail gr1
      FIGURE 1The principle pathways of early and advanced glycation (monosaccharide autoxidation/oxidative glycosylation, Namiki pathway, and glycoxidation). Arg, protein arginyl residue; 3-DG, 3-deoxyglycosone; Lys, protein lysyl residue; MG-H3, 2-amino-5-(2-amino-4-hydro-4-methyl-5-imidazolon-1-yl) pentanoic acid; R-NH2, side chain or N-terminal group in protein; R1/R2 is H/H for GO; H/CH3 for MGO; and H/C4H9O3 for 3-deoxyglycosone; Glarg, glyoxal-derived hydroimidazolone.
      Recently, protein glycation patterns were comprehensively characterized in human blood by a bottom-up liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic approach (
      • Frolov A.
      • Hoffmann R.
      Identification and relative quantification of specific glycation sites in human serum albumin.
      ,
      • Zhang Q.
      • Tang N.
      • Schepmoes A.A.
      • Phillips L.S.
      • Smith R.D.
      • Metz T.O.
      Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
      ). Thereby thousands of proteins were found to be glycated in hyperglycemic (diabetic) and healthy individuals (
      • Zhang Q.
      • Tang N.
      • Schepmoes A.A.
      • Phillips L.S.
      • Smith R.D.
      • Metz T.O.
      Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
      ,
      • Greifenhagen U.
      • Nguyen V.D.
      • Moschner J.
      • Giannis A.
      • Frolov A.
      • Hoffmann R.
      Sensitive and site-specific identification of carboxymethylated and carboxyethylated peptides in tryptic digests of proteins and human plasma.
      ,
      • Schmidt R.
      • Böhme D.
      • Singer D.
      • Frolov A.
      Specific tandem mass spectrometric detection of AGE-modified arginine residues in peptides.
      ,
      • Zhang Q.
      • Monroe M.E.
      • Schepmoes A.A.
      • Clauss T.R.
      • Gritsenko M.A.
      • Meng D.
      • Petyuk V.A.
      • Smith R.D.
      • Metz T.O.
      Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
      ). These glycation rates can be attributed to high blood glucose concentrations (>4.0 mm) and, therefore, high levels of Amadori product formation and monosaccharide autoxidation, especially in diabetic patients characterized with higher blood sugar concentrations (
      • Wolff S.P.
      • Dean R.T.
      Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes.
      ). Due to their ionic and/or cross-linking properties, AGEs strongly affect protein structure (
      • Morgan F.
      • Molle D.
      • Henry G.
      • Venien A.
      • Leonil J.
      • Peltre G.
      • Levieux D.
      • Maubois J.-L.
      • Bouhallab S.
      Glycation of bovine β-lactoglobulin: effect on the protein structure.
      ). Thus, glyoxal-derived hydroimidazolone (1-(-4-amino-4-carboxybutyl)-2-imino-5-oxoimidazolidine) and methylglyoxal-derived hydroimidazolone (MG-H) are cationic (
      • Schwarzenbolz U.
      • Henle T.
      • Haessner R.
      • Klostermeyer H.
      On the reaction of glyoxal with proteins.
      ,
      • Henle T.
      • Walter A.W.
      • Haessner R.
      • Klostermeyer H.
      Detection and identification of a protein-bound imidazolone resulting from the reaction of arginine residues and methylglyoxal.
      ), whereas Nϵ-carboxymethyl- (CML) and Nϵ-carboxyethyllysine (CEL) form anions in aqueous solution (
      • Ahmed M.U.
      • Thorpe S.R.
      • Baynes J.W.
      Identification of Nϵ-carboxymethyllysine as a degradation product of fructoselysine in glycated protein.
      ,
      • Ahmed M.U.
      • Brinkmann Frye E.
      • Degenhardt T.P.
      • Thorpe S.R.
      • Baynes J.W.
      Nϵ-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins.
      ). Moreover, both glyoxal and methylglyoxal form cationic lysine dimers, i.e. cross-links (
      • Ahmed N.
      • Thornalley P.J.
      Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and intrinsic fluorescence.
      ). As was previously demonstrated in animal models or in vitro studies, these changes directly affect specific biological functions: enzyme activities (
      • Yan H.
      • Harding J.J.
      Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase.
      ), affinity of transport polypeptides to their targets (
      • Baraka-Vidot J.
      • Guerin-Dubourg A.
      • Bourdon E.
      • Rondeau P.
      Impaired drug-binding capacities of in vitro and in vivo glycated albumin.
      ), ligand-receptor interaction (
      • Miele C.
      • Riboulet A.
      • Maitan M.A.
      • Oriente F.
      • Romano C.
      • Formisano P.
      • Giudicelli J.
      • Beguinot F.
      • Van Obberghen E.
      Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase Cα-mediated.
      ), and mechanical properties of contractile proteins (
      • Snow L.M.
      • Fugere N.A.
      • Thompson L.V.
      Advanced glycation end-product accumulation and associated protein modification in type II skeletal muscle with aging.
      ).
      In contrast to mammals, information on plant glycation is limited, although such systems (rich in highly reactive carbohydrates, e.g. fructose, ribose, and arabinose (
      • Syrový I.
      Glycation of albumin: reaction with glucose, fructose, galactose, ribose or glyceraldehyde measured using four methods.
      )), might have higher glycative potential. Moreover, plant tissues are rich in sugar phosphates, i.e. intermediates of glycolysis and the Calvin cycle (
      • Fortpied J.
      • Gemayel R.
      • Stroobant V.
      • van Schaftingen E.
      Plant ribulosamine/erythrulosamine 3-kinase, a putative protein-repair enzyme.
      ). Also it was demonstrated that triose phosphates (glyceraldehyde 3-phosphate and dihydroxyacetone phosphate) can be non-enzymatically converted to methylglyoxal (
      • Abordo E.A.
      • Minhas H.S.
      • Thornalley P.J.
      Accumulation of α-oxoaldehydes during oxidative stress: a role in cytotoxicity.
      ). Obviously, high concentrations of sugars in the presence of transition metal ions ensure high rates of monosaccharide autoxidation, production of reactive oxygen species (ROS), and AGE accumulation (
      • Zoccali C.
      • Mallamaci F.
      • Tripepi G.
      AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.
      ). The transport of electrons in mitochondria and chloroplasts, photorespiration pathway (especially under conditions of light and drought stress) (
      • Zoccali C.
      • Mallamaci F.
      • Tripepi G.
      AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.
      ), and ascorbate autoxidation (
      • Yamauchi Y.
      • Ejiri Y.
      • Tanaka K.
      AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.
      ) may also impact this process.
      Generally, the relevance of glycation in plants is indirectly supported not only by a high activity of ascorbate-glutathione cycle enzymes (
      • Chew O.
      • Whelan J.
      • Millar A.H.
      Molecular definition of the ascorbate-glutathione cycle in Arabidopsis mitochondria reveals dual targeting of antioxidant defenses in plants.
      ) but also by the existence of multiple antiglycative defense enzymes: glyoxalases I and II (
      • Singla-Pareek S.L.
      • Yadav S.K.
      • Pareek A.
      • Reddy M.K.
      • Sopory S.K.
      Enhancing salt tolerance in a crop plant by overexpression of glyoxalase II.
      ), ribulosamine/erythrulosamine 3-kinase (
      • Fortpied J.
      • Gemayel R.
      • Stroobant V.
      • van Schaftingen E.
      Plant ribulosamine/erythrulosamine 3-kinase, a putative protein-repair enzyme.
      ), and acylamino acid-releasing enzyme (
      • Yamauchi Y.
      • Ejiri Y.
      • Toyoda Y.
      • Tanaka K.
      Identification and biochemical characterization of plant acylamino acid-releasing enzyme.
      ). Recently, in their pioneer work, Bechtold et al. (
      • Bechtold U.
      • Rabbani N.
      • Mullineaux P.M.
      • Thornalley P.J.
      Quantitative measurement of specific biomarkers for protein oxidation, nitration and glycation in Arabidopsis leaves.
      ) detected AGE-modified amino acids in protein hydrolysates obtained from Arabidopsis thaliana leaves. However, the plant protein glycation targets and exact modification sites therein are still unknown. Hence, no assumptions concerning physiological effects and mechanisms of plant glycation could be made. Therefore, here we present the first comprehensive in-depth analysis of a glycated proteome from a crop plant species, Brassica napus, using A. thaliana as a reference organism. Based on the modification patterns and metabolomics data, the pathways of AGE formation and possible glycation agents in plants are proposed. The potential glycation agents of the plant origin were investigated for their relative reactivity in vitro and their possible impact on the generation of AGEs in vivo.

      Author Contributions

      E. L., D. B., U. G., J. M., A. F., C. M., and N. O. designed and performed plant experiments and stress characterization. E. L., T. B., and A. F. designed and performed proteomic experiments. T. B., E. T., G. P., and C. B. designed and performed metabolomic experiments. U. G., E. L., N. F., G. U. B., and A. F. performed in vitro experiments with model peptides. E. L., C. M., A. T., C. B., T. V., L. A. W., and A. F. interpreted data and wrote the manuscript.

      Acknowledgments

      We thank Prof. Dr. Ralf Hoffmann (Universität Leipzig, Germany) for providing laboratory facilities as well as Rico Schmidt (Martin Luther University Halle-Wittenberg, Germany) and Nick Bergau (Leibniz Institute of Plant Biochemistry) for support with peptide synthesis and LC-QqTOF-MS experiments, respectively. We also thank Sandro Spiller and Sanja Milkovska-Stamenova (Universität Leipzig) for help with the plant experiments as well as Nikita Shiljaev (University of St. Petersburg) for help with interpretation of the in vitro data.

      References

        • Ulrich P.
        • Cerami A.
        Protein glycation, diabetes, and aging.
        Recent Prog. Horm. Res. 2001; 56: 1-21
        • Hodge J.E.
        The Amadori rearrangement.
        Adv. Carbohydr. Chem. 1955; 10: 169-205
        • Heyns K.
        • Noack H.
        Die umsetzung von D-fructose mit L-lysine und L-arginin und deren beziehung zu nichtenzymatischen bräunungsreaktionen.
        Chem. Ber. 1962; 95: 720-727
        • Grillo M.A.
        • Colombatto S.
        Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases.
        Amino Acids. 2008; 35: 29-36
        • Wolff S.P.
        • Dean R.T.
        Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes.
        Biochem. J. 1987; 245: 243-250
        • Wolff S.P.
        • Dean R.T.
        Aldehydes and dicarbonyls in non-enzymic glycosylation of proteins.
        Biochem. J. 1988; 249: 618-619
        • Frolov A.
        • Schmidt R.
        • Spiller S.
        • Greifenhagen U.
        • Hoffmann R.
        Formation of arginine-derived advanced glycation end products in peptide-glucose mixtures during boiling.
        J. Agric. Food Chem. 2014; 62: 3626-3635
        • Luevano-Contreras C.
        • Chapman-Novakofski K.
        Dietary advanced glycation end products and ageing.
        Nutrients. 2010; 2: 1247-1265
        • Herold K.
        • Moser B.
        • Chen Y.
        • Zeng S.
        • Yan S.F.
        • Ramasamy R.
        • Emond J.
        • Clynes R.
        • Schmidt A.M.
        Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress.
        J. Leukoc. Biol. 2007; 82: 204-212
        • Frolov A.
        • Hoffmann R.
        Identification and relative quantification of specific glycation sites in human serum albumin.
        Anal. Bioanal. Chem. 2010; 397: 2349-2356
        • Zhang Q.
        • Tang N.
        • Schepmoes A.A.
        • Phillips L.S.
        • Smith R.D.
        • Metz T.O.
        Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
        J. Proteome Res. 2008; 7: 2025-2032
        • Greifenhagen U.
        • Nguyen V.D.
        • Moschner J.
        • Giannis A.
        • Frolov A.
        • Hoffmann R.
        Sensitive and site-specific identification of carboxymethylated and carboxyethylated peptides in tryptic digests of proteins and human plasma.
        J. Proteome Res. 2015; 14: 768-777
        • Schmidt R.
        • Böhme D.
        • Singer D.
        • Frolov A.
        Specific tandem mass spectrometric detection of AGE-modified arginine residues in peptides.
        J. Mass Spectrom. 2015; 50: 613-624
        • Zhang Q.
        • Monroe M.E.
        • Schepmoes A.A.
        • Clauss T.R.
        • Gritsenko M.A.
        • Meng D.
        • Petyuk V.A.
        • Smith R.D.
        • Metz T.O.
        Proteomic profiling of nonenzymatically glycated proteins in human plasma and erythrocyte membranes.
        J. Proteome Res. 2011; 10: 3076-3088
        • Morgan F.
        • Molle D.
        • Henry G.
        • Venien A.
        • Leonil J.
        • Peltre G.
        • Levieux D.
        • Maubois J.-L.
        • Bouhallab S.
        Glycation of bovine β-lactoglobulin: effect on the protein structure.
        Int. J. Food Sci. Technol. 1999; 34: 429-435
        • Schwarzenbolz U.
        • Henle T.
        • Haessner R.
        • Klostermeyer H.
        On the reaction of glyoxal with proteins.
        Z. Lebensm. Unters. Forsch. A. 1997; 205: 121-124
        • Henle T.
        • Walter A.W.
        • Haessner R.
        • Klostermeyer H.
        Detection and identification of a protein-bound imidazolone resulting from the reaction of arginine residues and methylglyoxal.
        Z. Lebensm. Unters. Forsch. 1994; 199: 55-58
        • Ahmed M.U.
        • Thorpe S.R.
        • Baynes J.W.
        Identification of Nϵ-carboxymethyllysine as a degradation product of fructoselysine in glycated protein.
        J. Biol. Chem. 1986; 261: 4889-4894
        • Ahmed M.U.
        • Brinkmann Frye E.
        • Degenhardt T.P.
        • Thorpe S.R.
        • Baynes J.W.
        Nϵ-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins.
        Biochem. J. 1997; 324: 565-570
        • Ahmed N.
        • Thornalley P.J.
        Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and intrinsic fluorescence.
        Biochem. J. 2002; 364: 15-24
        • Yan H.
        • Harding J.J.
        Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase.
        Biochem. J. 1997; 328: 599-605
        • Baraka-Vidot J.
        • Guerin-Dubourg A.
        • Bourdon E.
        • Rondeau P.
        Impaired drug-binding capacities of in vitro and in vivo glycated albumin.
        Biochimie. 2012; 94: 1960-1967
        • Miele C.
        • Riboulet A.
        • Maitan M.A.
        • Oriente F.
        • Romano C.
        • Formisano P.
        • Giudicelli J.
        • Beguinot F.
        • Van Obberghen E.
        Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate (IRS) signaling through a protein kinase Cα-mediated.
        J. Biol. Chem. 2003; 278: 47376-47387
        • Snow L.M.
        • Fugere N.A.
        • Thompson L.V.
        Advanced glycation end-product accumulation and associated protein modification in type II skeletal muscle with aging.
        J. Gerontol. A Biol. Sci. Med. Sci. 2007; 62: 1204-1210
        • Syrový I.
        Glycation of albumin: reaction with glucose, fructose, galactose, ribose or glyceraldehyde measured using four methods.
        J. Biochem. Biophys. Methods. 1994; 28: 115-121
        • Fortpied J.
        • Gemayel R.
        • Stroobant V.
        • van Schaftingen E.
        Plant ribulosamine/erythrulosamine 3-kinase, a putative protein-repair enzyme.
        Biochem. J. 2005; 388: 795-802
        • Abordo E.A.
        • Minhas H.S.
        • Thornalley P.J.
        Accumulation of α-oxoaldehydes during oxidative stress: a role in cytotoxicity.
        Biochem. Pharmacol. 1999; 58: 641-648
        • Zoccali C.
        • Mallamaci F.
        • Tripepi G.
        AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.
        Nephrol. Dial. Transplant. 2000; 15: 7-11
        • Yamauchi Y.
        • Ejiri Y.
        • Tanaka K.
        AGEs and carbonyl stress: potential pathogenetic factors of long-term uraemic complications.
        Plant Cell Physiol. 2002; 43: 1334-1341
        • Chew O.
        • Whelan J.
        • Millar A.H.
        Molecular definition of the ascorbate-glutathione cycle in Arabidopsis mitochondria reveals dual targeting of antioxidant defenses in plants.
        J. Biol. Chem. 2003; 278: 46869-46877
        • Singla-Pareek S.L.
        • Yadav S.K.
        • Pareek A.
        • Reddy M.K.
        • Sopory S.K.
        Enhancing salt tolerance in a crop plant by overexpression of glyoxalase II.
        Transgenic Res. 2008; 17: 171-180
        • Yamauchi Y.
        • Ejiri Y.
        • Toyoda Y.
        • Tanaka K.
        Identification and biochemical characterization of plant acylamino acid-releasing enzyme.
        J. Biochem. 2003; 134: 251-257
        • Bechtold U.
        • Rabbani N.
        • Mullineaux P.M.
        • Thornalley P.J.
        Quantitative measurement of specific biomarkers for protein oxidation, nitration and glycation in Arabidopsis leaves.
        Plant J. 2009; 59: 661-671
        • Greifenhagen U.
        • Frolov A.
        • Hoffmann R.
        Oxidative degradation of N-fructosylamine-substituted peptides in heated aqueous systems.
        Amino Acids. 2015; 47: 1065-1076
        • Rich D.H.
        • Singh J.
        The carbodiimide method.
        in: Gross E. Meinenhofer J. The Peptides. Academic Press, New York1979: 241-314
        • Griffiths G.
        • Leverentz M.
        • Silkowski H.
        • Gill N.
        • Sánchez-Serrano J.J.
        Lipid hydroperoxide levels in plant tissues.
        J. Exp. Bot. 2000; 51: 1363-1370
        • Huang C.
        • He W.
        • Guo J.
        • Chang X.
        • Su P.
        • Zhang L.
        Increased sensitivity to salt stress in an ascorbate-deficient Arabidopsis mutant.
        J. Exp. Bot. 2005; 56: 3041-3049
        • Frolov A.
        • Blüher M.
        • Hoffmann R.
        Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus.
        Anal. Bioanal. Chem. 2014; 406: 5755-5763
        • Bollineni R.C.
        • Fedorova M.
        • Blüher M.
        • Hoffmann R.
        Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus.
        J. Proteome. Res. 2014; 13: 5081-5093
        • Frolov A.
        • Hoffmann R.
        Analysis of Amadori peptides enriched by boronic acid affinity chromatography.
        Ann. N.Y. Acad. Sci. 2008; 1126: 253-256
        • Milkovska-Stamenova S.
        • Schmidt R.
        • Frolov A.
        • Birkemeyer C.
        GC-MS method for the quantitation of carbohydrate intermediates in glycation systems.
        J. Agric. Food Chem. 2015; 63: 5911-5919
        • Cellar N.A.
        • Kuppannan K.
        • Langhorst M.L.
        • Ni W.
        • Xu P.
        • Young S.A.
        Cross species applicability of abundant protein depletion columns for ribulose-1,5-bisphosphate carboxylase/oxygenase.
        J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2008; 861: 29-39
        • Bou R.
        • Codony R.
        • Tres A.
        • Decker E.A.
        • Guardiola F.
        Determination of hydroperoxides in foods and biological samples by the ferrous oxidation-xylenol orange method: a review of the factors that influence the method's performance.
        Anal. Biochem. 2008; 377: 1-15
        • Singer D.
        • Kuhlmann J.
        • Muschket M.
        • Hoffmann R.
        Separation of multiphosphorylated peptide isomers by hydrophilic interaction chromatography on an aminopropyl phase.
        Anal. Chem. 2010; 82: 6409-6414
        • Ahmed N.
        • Babaei-Jadidi R.
        • Howell S.K.
        • Thornalley P.J.
        • Beisswenger P.J.
        Glycated and oxidized protein degradation products are indicators of fasting and postprandial hyperglycemia in diabetes.
        Diabetes Care. 2005; 28: 2465-2471
        • Rabbani N.
        • Thornalley P.J.
        The dicarbonyl proteome: proteins susceptible to dicarbonyl glycation at functional sites in health, aging, and disease.
        Ann. N.Y. Acad. Sci. 2008; 1126: 124-127
        • Semba R.D.
        • Nicklett E.J.
        • Ferrucci L.
        Does accumulation of advanced glycation end products contribute to the aging phenotype?.
        J. Gerontol. A Biol. Sci. Med. Sci. 2010; 65: 963-975
        • Sebeková K.
        • Schinzel R.
        • Ling H.
        • Simm A.
        • Xiang G.
        • Gekle M.
        • Münch G.
        • Vamvakas S.
        • Heidland A.
        Advanced glycated albumin impairs protein degradation in the kidney proximal tubules cell line LLC-PK1.
        Cell. Mol. Biol. 1998; 44: 1051-1060
        • Wells-Knecht K.J.
        • Zyzak D.V.
        • Litchfield J.E.
        • Thorpe S.R.
        • Baynes J.W.
        Pathways of formation of glycoxidation products during glycation of collagen.
        Biochemistry. 1995; 34: 3702-3709
        • Hayashi T.
        • Namiki M.
        Formation of two-carbon sugar fragment at an early stage of the browning reaction of sugar with amine.
        Agric. Biol. Chem. 1980; 44: 2575-2580
        • Weiss M.F.
        • Erhard P.
        • Kader-Attia F.A.
        • Wu Y.C.
        • Deoreo P.B.
        • Araki A.
        • Glomb M.A.
        • Monnier V.M.
        Mechanisms for the formation of glycoxidation products in end-stage renal disease.
        Kidney Int. 2000; 57: 2571-2585
        • Poulsen M.W.
        • Hedegaard R.V.
        • Andersen J.M.
        • de Courten B.
        • Bügel S.
        • Nielsen J.
        • Skibsted L.H.
        • Dragsted L.O.
        Advanced glycation endproducts in food and their effects on health.
        Food Chem. Toxicol. 2013; 60: 10-37
        • Hamada Y.
        • Araki N.
        • Koh N.
        • Nakamura J.
        • Horiuchi S.
        • Hotta N.
        Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway.
        Biochem. Biophys. Res. Commun. 1996; 228: 539-543
        • Hori M.
        • Yagi M.
        • Nomoto K.
        • Ichijo R.
        • Shimode A.
        • Kitano T.
        • Yonei Y.
        Experimental models for advanced glycation end product formation using albumin, collagen, elastin, keratin and proteoglycan.
        Anti-aging Med. 2012; 9: 125-134
        • Manini P.
        • La Pietra P.
        • Panzella L.
        • Napolitano A.
        • d'Ischia M.
        Glyoxal formation by Fenton-induced degradation of carbohydrates and related compounds.
        Carbohydr. Res. 2006; 341: 1828-1833