title: Glycation of the high affinity NGF-receptor and RAGE leads to reduced ligand affinity.
abstract: AGEs are posttranslational modifications generated by irreversible non-enzymatic crosslinking reactions between sugars and proteins - a reaction referred to as glycation. Glycation, a feature of ageing, can lead to non-degradable and less functional proteins and enzymes and can additionally induce inflammation and further pathophysiological processes such as neurodegeneration. In this study we investigated the influence of glycation on the high affinity NGF-receptor TrkA and the AGE-receptor RAGE. We quantified the binding affinity of the TrkA-receptor and RAGE to their ligands by surface plasmon resonance (SPR) and compared these to the binding affinity after glycation. At the same time, we established a glycation procedure using SPR. We found that glycation of TrkA reduced the affinity to NGF by a factor of three, which could be shown to lead to a reduction of NGF-dependent neurite outgrowth in PC12 cells. Glycation of RAGE reduced binding affinity of AGEs by 10-fold.
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Saale), Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Bennmann
authors.affiliation: Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Walther-Nernst-Str. 3, D-12489 Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kannicht
authors.affiliation: Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Walther-Nernst-Str. 3, D-12489 Berlin, Germany.
authors.forename: Claudine
authors.initials: C
authors.lastname: Fisseau
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jacobs
authors.affiliation: Center for Medical Basic Research of the Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarette-Santos
authors.affiliation: Clinic and Policlinic for Cardiothoracic Surgery, University Hospital Halle, Ernst-Grube-Str. 40, D-06120 Halle (Saale), Germany.
authors.forename: Britt
authors.initials: B
authors.lastname: Hofmann
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Saale), Germany. Electronic address: ruediger.horstkorte@medizin.uni-halle.de.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
mesh_terms: D000818:Animals; D006031:Glycosylation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C000593874:Ager protein, rat; D009419:Nerve Tissue Proteins; D000067759:Receptor for Advanced Glycation End Products; D017978:Receptors, Growth Factor; C068313:Ngfr protein, rat
keywords: Advanced glycation endproducts (AGEs); Binding affinity; Glycation; Neuronal plasticity; RAGE; TrkA