title: Ionising radiation induces persistent alterations in the cardiac mitochondrial function of C57BL/6 mice 40 weeks after local heart exposure.
abstract: OBJECTIVE
  Radiotherapy of thoracic and chest-wall tumours increases the long-term risk of radiation-induced heart disease. The aim of this study was to investigate the long-term effect of local heart irradiation on cardiac mitochondria.
  
  
  METHODS
  C57BL/6 and atherosclerosis-prone ApoE(-/-) mice received local heart irradiation with a single X-ray dose of 2 Gy. To investigate the low-dose effect, C57BL/6 mice also received a single heart dose of 0.2 Gy. Functional and proteomic alterations of cardiac mitochondria were evaluated after 40 weeks, compared to age-matched controls.
  
  
  RESULTS
  The respiratory capacity of irradiated C57BL/6 cardiac mitochondria was significantly reduced at 40 weeks. In parallel, protein carbonylation was increased, suggesting enhanced oxidative stress. Considerable alterations were found in the levels of proteins of mitochondria-associated cytoskeleton, respiratory chain, ion transport and lipid metabolism. Radiation induced similar but less pronounced effects in the mitochondrial proteome of ApoE(-/-) mice. In ApoE(-/-), no significant change was observed in mitochondrial respiration or protein carbonylation. The dose of 0.2 Gy had no significant effects on cardiac mitochondria.
  
  
  CONCLUSIONS
  This study suggests that ionising radiation causes non-transient alterations in cardiac mitochondria, resulting in oxidative stress that may ultimately lead to malfunctioning of the heart muscle.
authors.affiliation: Institute of Radiation Biology, German Research Center for Environmental Health, Neuherberg, Germany. zarko.barjaktarovic@helmholtz-muenchen.de
authors.forename: Zarko
authors.initials: Z
authors.lastname: Barjaktarovic
authors.forename: Alena
authors.initials: A
authors.lastname: Shyla
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.forename: Sabine
authors.initials: S
authors.lastname: Schulz
authors.forename: Julia
authors.initials: J
authors.lastname: Haagen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
authors.forename: Hakan
authors.initials: H
authors.lastname: Sarioglu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Hans
authors.initials: H
authors.lastname: Zischka
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D006321:Heart / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress; D050050:Protein Carbonylation; D011839:Radiation, Ionizing; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E