title: Rapid proteomic remodeling of cardiac tissue caused by total body ionizing radiation.
abstract: Accidental nuclear scenarios lead to environmental contamination of unknown level. Immediate radiation-induced biological responses that trigger processes leading to adverse health effects decades later are not well understood. A comprehensive proteomic analysis provides a promising means to identify and quantify the initial damage after radiation exposure. Early changes in the cardiac tissue of C57BL/6 mice exposed to total body irradiation were studied, using a dose relevant to both intentional and accidental exposure (3 Gy gamma ray). Heart tissue protein lysates were analyzed 5 and 24 h after the exposure using isotope-coded protein labeling (ICPL) and 2-dimensional difference-in-gel-electrophoresis (2-D DIGE) proteomics approaches. The differentially expressed proteins were identified by LC-ESI-MS-MS. Both techniques showed similar functional groups of proteins to be involved in the initial injury. Pathway analyses indicated that total body irradiation immediately induced biological responses such as inflammation, antioxidative defense, and reorganization of structural proteins. Mitochondrial proteins represented the protein class most sensitive to ionizing radiation. The proteins involved in the initial damage processes map to several functional categories involving cardiotoxicity. This prompts us to propose that these early changes are indicative of the processes that lead to an increased risk of cardiovascular disease after radiation exposure.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany. omid.azimzadeh@helmholtz-muenchen.de
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.forename: Hakan
authors.initials: H
authors.lastname: Sarioglu
authors.forename: Zarko
authors.initials: Z
authors.lastname: Barjaktarovic
authors.forename: Marcus
authors.initials: M
authors.lastname: Conrad
authors.forename: Andreas
authors.initials: A
authors.lastname: Vogt
authors.forename: Julia
authors.initials: J
authors.lastname: Calzada-Wack
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.forename: Michaela
authors.initials: M
authors.lastname: Aubele
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000818:Animals; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005720:Gamma Rays / Q000009:adverse effects*; D006321:Heart / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000528:radiation effects; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D050050:Protein Carbonylation / Q000528:radiation effects; D025941:Protein Interaction Mapping; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000528:radiation effects*; D040901:Proteomics; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D020257:Ventricular Remodeling / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: D011506:Proteins; D020543:Proteome