title: Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.
abstract: Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University , Washington DC 20057, United States.
authors.forename: Evagelia C
authors.initials: EC
authors.lastname: Laiakis
authors.forename: Katrin
authors.initials: K
authors.lastname: Strassburg
authors.forename: Ralf
authors.initials: R
authors.lastname: Bogumil
authors.forename: Steven
authors.initials: S
authors.lastname: Lai
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: James
authors.initials: J
authors.lastname: Langridge
authors.forename: Robert S
authors.initials: RS
authors.lastname: Plumb
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
mesh_terms: D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000097:blood* / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000528:radiation effects*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011839:Radiation, Ionizing
chemical_list: D015525:Fatty Acids, Omega-3