title: Total body exposure to low-dose ionizing radiation induces long-term alterations to the liver proteome of neonatally exposed mice.
abstract: Tens of thousands of people are being exposed daily to environmental low-dose gamma radiation. Epidemiological data indicate that such low radiation doses may negatively affect liver function and result in the development of liver disease. However, the biological mechanisms behind these adverse effects are unknown. The aim of this study was to investigate radiation-induced damage in the liver after low radiation doses. Neonatal male NMRI mice were exposed to total body irradiation on postnatal day 10 using acute single doses ranging from 0.02 to 1.0 Gy. Early (1 day) and late (7 months) changes in the liver proteome were tracked using isotope-coded protein label technology and quantitative mass spectrometry. Our data indicate that low and moderate radiation doses induce an immediate inhibition of the glycolysis pathway and pyruvate dehydrogenase availability in the liver. Furthermore, they lead to significant long-term alterations in lipid metabolism and increased liver inflammation accompanying inactivation of the transcription factor peroxisome proliferator-activated receptor alpha. This study contributes to the understanding of the potential risk of liver damage in populations environmentally exposed to ionizing radiation.
authors.affiliation: Institute of Radiation Biology, ‡Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health , 85764 Neuherberg, Germany.
authors.forename: Mayur V
authors.initials: MV
authors.lastname: Bakshi
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.forename: Zarko
authors.initials: Z
authors.lastname: Barjaktarovic
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.forename: Sonja
authors.initials: S
authors.lastname: Buratovic
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D019295:Computational Biology; D004307:Dose-Response Relationship, Radiation; D015151:Immunoblotting; D050356:Lipid Metabolism / Q000528:radiation effects; D008099:Liver / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D020543:Proteome / Q000378:metabolism* / Q000528:radiation effects*; D040901:Proteomics; D011839:Radiation, Ionizing; D053719:Tandem Mass Spectrometry; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D020543:Proteome
keywords: ICPL; Low-dose ionizing radiation; PPAR alpha; liver; metabolic crosstalk; proteomics