title: Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients.
abstract: Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (>10 years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2-5 years, n = 20) and long disease duration (>10 years, n = 20) did not reveal any significant differences.
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.|Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Greifenhagen
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.|Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Frolov
authors.affiliation: Endocrinology, Department of Medicine, Universität Leipzig, Liebigstraße 20, 04103, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany. bioanaly@rz.uni-leipzig.de.|Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany. bioanaly@rz.uni-leipzig.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D001665:Binding Sites; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000737:chemistry; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D017127:Glycation End Products, Advanced
keywords: Advanced glycation end product (AGE); Mass spectrometry; Non-enzymatic modification; Posttranslational modification (PTM); Proteomics; Type 2 diabetes mellitus (T2DM)