title: Oxidative lipidomics of γ-radiation-induced lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation.
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.
authors.affiliation: Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA, USA. yyt1@pitt.edu
authors.forename: Yulia Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: Valentyna I
authors.initials: VI
authors.lastname: Kapralova
authors.forename: Karla
authors.initials: K
authors.lastname: Wasserloos
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Mosher
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Pitt
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002308:Cardiolipins / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D020404:Glycerophospholipids / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000528:radiation effects*; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D002308:Cardiolipins; D020404:Glycerophospholipids; D010718:Phosphatidylserines