title: Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines.
abstract: Glycation and glycoxidation of proteins and peptides have been intensively studied and are considered as reliable diagnostic biomarkers of hyperglycemia and early stages of type II diabetes. However, glucose can also react with primary amino groups present in other cellular components, such as aminophospholipids (aminoPLs). Although it is proposed that glycated aminoPLs can induce many cellular responses and contribute to the development and progression of diabetes, the routes of their formation and their biological roles are only partially revealed. The same is true for the influence of glucose-derived modifications on the biophysical properties of PLs. Here we studied structural, signaling, and biophysical properties of glycated and glycoxidized phosphatidylethanolamines (PEs). By combining high resolution mass spectrometry and nuclear magnetic resonance spectroscopy it was possible to deduce the structures of several intermediates indicating an oxidative cleavage of the Amadori product yielding glycoxidized PEs including advanced glycation end products, such as carboxyethyl- and carboxymethyl-ethanolamines. The pro-oxidative role of glycated PEs was demonstrated and further associated with several cellular responses including activation of NFκB signaling pathways. Label free proteomics indicated significant alterations in proteins regulating cellular metabolisms. Finally, the biophysical properties of PL membranes changed significantly upon PE glycation, such as melting temperature (Tm), membrane surface charge, and ion transport across the phospholipid bilayer.
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Germany; Center for Biotechnology and Biomedicine, Universität Leipzig, Germany; Institute for Medical Physics and Biophysics, Faculty of Medicine, Universität Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Annibal
authors.affiliation: Institute for Medical Physics and Biophysics, Faculty of Medicine, Universität Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Riemer
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics; University of Veterinary Medicine Vienna, Austria.
authors.forename: Olga
authors.initials: O
authors.lastname: Jovanovic
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Germany; Center for Biotechnology and Biomedicine, Universität Leipzig, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Westphal
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Germany; Center for Biotechnology and Biomedicine, Universität Leipzig, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Griesser
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics; University of Veterinary Medicine Vienna, Austria.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Pohl
authors.affiliation: Institute for Medical Physics and Biophysics, Faculty of Medicine, Universität Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Germany; Center for Biotechnology and Biomedicine, Universität Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, Universität Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Germany; Center for Biotechnology and Biomedicine, Universität Leipzig, Germany. Electronic address: maria.fedorova@bbz.uni-leipzig.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Fedorova
mesh_terms: D055592:Biophysical Phenomena; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000737:chemistry* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000737:chemistry* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics
chemical_list: D017127:Glycation End Products, Advanced; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D005947:Glucose
keywords: Advanced glycation end products (AGE); Aminophospholipids glycation; Cellular metabolism; Mass spectrometry; Membrane surface charge; NMR spectroscopy