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Rapid proteomic remodeling of cardiac tissue caused by total body ionizing radiation
Authors:Azimzadeh Omid  Scherthan Harry  Sarioglu Hakan  Barjaktarovic Zarko  Conrad Marcus  Vogt Andreas  Calzada-Wack Julia  Neff Frauke  Aubele Michaela  Buske Christian  Atkinson Michael J  Tapio Soile
Institution:Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany. omid.azimzadeh@helmholtz-muenchen.de
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.
Keywords:Cardiac disease  Cell biology  2‐D DIGE  Ionizing irradiation  Isotope‐coded protein labeling  Oxidative stress
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