Characterization of the glycated human cerebrospinal fluid proteome

Article Article scientifique Article Characterization of the glycated human cerebrospinal fluid proteome eng 2012 author Ramirez Boo Maria 701190 author Priego Capote Feliciano 665394 author Hainard Alexandre 0009-0006-7403-3261 635700 author Gluck Florent 126541 author Burkhard Pierre 0000-0002-7459-5778 92389 author Sanchez Jean-Charles 0000-0002-8733-5932 24399 4766-4782 10.1016/j.jprot.2012.01.017 22300578 1874-3919 Protein glycation is a nonenzymatic modification that involves pathological functions in neurological diseases. Despite the high number of studies showing accumulation of advanced end glycation products (AGEs) at clinical stage, there is a lack of knowledge about which proteins are modified, where those modifications occur, and to what extent. The goal of this study was to achieve a comprehensive characterization of proteins modified by early glycation in human cerebrospinal fluid (CSF). Approaches based on glucose diferential labeling and mass spectrometry have been applied to evaluate the glycated CSF proteome at two physiological conditions: native glucose level and in vitro high glucose content. For both purposes, detection of glycated proteins was carried out by HCD-MS2 and CID-MS3 modes after endoproteinase Glu-C digestion and boronate affinity chromatography. The abundance of glycation was assessed by protein labeling with (13)C(6)-glucose incubation. The analysis of native glycated CSF identified 111 glycation sites corresponding to 48 glycated proteins. Additionally, the in vitro high glucose level approach detected 265 glycation sites and 101 glycated proteins. The comparison of glycation levels under native and 15 mM glucose conditions showed relative concentration increases up to ten folds for some glycated proteins. This report revealed for the first time a number of key glycated CSF proteins known to be involved in neuroinflammation and neurodegenerative disorders. Altogether, the present study contains valuable and unique information, which should further help to clarify the pathological role of glycation in central nervous system pathologies. This article is part of a Special Issue entitled: Translational Proteomics. Aged, 80 and over Central Nervous System Diseases/cerebrospinal fluid Glucose/metabolism Glycoproteins/cerebrospinal fluid Glycosylation Humans Male Mass Spectrometry/methods Proteome/metabolism Proteomics/methods Dewey 576 136 Département de biologie structurale et bioinformatique 21E false 124 Groupe Pierre Burkhard (neurologie) 154 369 Biomarqueurs 635 Journal of proteomics 75 15 b9c033ef-d7eb-40a4-9d4f-f83eb02a8565 Article (Published version) Restricted Ramirez-Boo-2012-Characterization of.pdf 1937610 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de biologie structurale et bioinformatique

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Characterization of the glycated human cerebrospinal fluid proteome	Journal of proteomics			2012	642	1

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Ramirez Boo, Maria