Ion-trap tandem mass spectrometric analysis of Amadori-glycated phosphatidylethanolamine in human plasma with or without diabetes

J Lipid Res. 2005 Nov;46(11):2514-24. doi: 10.1194/jlr.D500025-JLR200. Epub 2005 Sep 8.

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.

MeSH terms

  • Adult
  • Aged
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 2 / blood*
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Lipid Peroxidation
  • Lipids / chemistry
  • Mass Spectrometry / instrumentation
  • Mass Spectrometry / methods*
  • Middle Aged
  • Models, Chemical
  • Oxidative Stress
  • Phosphatidylcholines / biosynthesis
  • Phosphatidylethanolamines / chemistry*
  • Phosphatidylserines / chemistry
  • Phospholipids / chemistry
  • Reactive Oxygen Species

Substances

  • Glycation End Products, Advanced
  • Lipids
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Phosphatidylserines
  • Phospholipids
  • Reactive Oxygen Species
  • phosphatidylcholine hydroperoxide
  • phosphatidylethanolamine hydroperoxide
  • phosphatidylethanolamine