title: Ion-trap tandem mass spectrometric analysis of Amadori-glycated phosphatidylethanolamine in human plasma with or without diabetes.
abstract: Peroxidized phospholipid-mediated cytotoxicity is involved in the pathophysiology of diseases [i.e., an abnormal increase of phosphatidylcholine hydroperoxide (PCOOH) in plasma of type 2 diabetic patients]. The PCOOH accumulation may relate to Amadori-glycated phosphatidylethanolamine (Amadori-PE; deoxy-D-fructosyl phosphatidylethanolamine), because Amadori-PE causes oxidative stress. However, the occurrence of lipid glycation products, including Amadori-PE, in vivo is still unclear. Consequently, we developed an analysis method of Amadori-PE using a quadrupole/linear ion-trap mass spectrometer, the Applied Biosystems QTRAP. In positive ion mode, collision-induced dissociation of Amadori-PE produced a well-characterized diglyceride ion ([M+H-303]+) permitting neutral loss scanning and multiple reaction monitoring (MRM). When lipid extract from diabetic plasma was infused directly into the QTRAP, Amadori-PE molecular species could be screened out by neutral loss scanning. Interfacing liquid chromatography with QTRAP mass spectrometry enabled the separation and determination of predominant plasma Amadori-PE species with sensitivity of approximately 0.1 pmol/injection in MRM. The plasma Amadori-PE level was 0.08 mol% of total PE in healthy subjects and 0.15-0.29 mol% in diabetic patients. Furthermore, plasma Amadori-PE levels were positively correlated with PCOOH (a maker for oxidative stress). These results show the involvement between lipid glycation and lipid peroxidation in diabetes pathogenesis.
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Oak
authors.forename: Ohki
authors.initials: O
authors.lastname: Higuchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Otani
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Mune
authors.forename: Hua
authors.initials: H
authors.lastname: Cai
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D008875:Middle Aged; D008956:Models, Chemical; D018384:Oxidative Stress; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D017382:Reactive Oxygen Species
chemical_list: D017127:Glycation End Products, Advanced; D008055:Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D017382:Reactive Oxygen Species; C057590:phosphatidylcholine hydroperoxide; C027850:phosphatidylethanolamine hydroperoxide; C483858:phosphatidylethanolamine