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Oxidative lipidomics of γ-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation

Radiat Res. 2011 May;175(5):610-21. doi: 10.1667/RR2297.1. Epub 2011 Feb 21.

Abstract

Oxidative damage plays a significant role in the pathogenesis of γ-radiation-induced lung injury. Endothelium is a preferred target for early radiation-induced damage and apoptosis. Given the newly discovered role of oxidized phospholipids in apoptotic signaling, we performed oxidative lipidomics analysis of phospholipids in irradiated mouse lungs and cultured mouse lung endothelial cells. C57BL/6NHsd female mice were subjected to total-body irradiation (10 Gy, 15 Gy) and euthanized 24 h thereafter. Mouse lung endothelial cells were analyzed 48 h after γ irradiation (15 Gy). We found that radiation-induced apoptosis in vivo and in vitro was accompanied by non-random oxidation of phospholipids. Cardiolipin and phosphatidylserine were the major oxidized phospholipids, while more abundant phospholipids (phosphatidylcholine, phosphatidylethanolamine) remained non-oxidized. Electrospray ionization mass spectrometry analysis revealed the formation of cardiolipin and phosphatidylserine oxygenated molecular species in the irradiated lung and cells. Analysis of fatty acids after hydrolysis of cardiolipin and phosphatidylserine by phospholipase A(2) revealed the presence of mono-hydroperoxy and/or mono-hydroxy/mono-epoxy, mono-hydroperoxy/mono-oxo molecular species of linoleic acid. We speculate that cyt c-driven oxidations of cardiolipin and phosphatidylserine associated with the execution of apoptosis in pulmonary endothelial cells are important contributors to endothelium dysfunction in γ-radiation-induced lung injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cardiolipins / metabolism
  • Computational Biology / methods*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Endothelial Cells / radiation effects
  • Female
  • Gamma Rays / adverse effects*
  • Glycerophospholipids / metabolism*
  • Lipid Peroxidation / radiation effects*
  • Lung / chemistry
  • Lung / metabolism
  • Lung / radiation effects
  • Lung Injury / metabolism*
  • Lung Injury / pathology
  • Mice
  • Phosphatidylserines / metabolism
  • Radiation Injuries, Experimental / metabolism*
  • Radiation Injuries, Experimental / pathology
  • Spectrometry, Mass, Electrospray Ionization*
  • Whole-Body Irradiation / adverse effects

Substances

  • Cardiolipins
  • Glycerophospholipids
  • Phosphatidylserines