In-Utero Low-Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome.
Prenatal exposure to stress such as increased level of reactive oxygen species or antiviral therapy are known factors leading to adult heart defects. The risks following a radiation exposure during fetal period are unknown, as are the mechanisms of any potential cardiac damage. The aim of this study was to gather evidence for possible damage by investigating long-term changes in the mouse heart proteome after prenatal exposure to low and moderate radiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a single total body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring were sacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissue was performed using Isotope Coded Protein Label technology and tandem mass spectrometry. The proteomics data were analyzed by bioinformatics and key changes were validated by immunoblotting. Persistent changes were observed in the expression of proteins representing mitochondrial respiratory complexes, redox and heat shock response, and the cytoskeleton, even at the low dose of 0.1 Gy. The level of total and active form of the kinase MAP4K4 that is essential for the embryonic development of mouse heart was persistently decreased at the radiation dose of 1.0 Gy. This study provides the first insight into the molecular mechanisms of cardiac impairment induced by ionizing radiation exposure during the prenatal period.
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, D-85764 Neuherberg, Germany.
Mayur V
MV
Bakshi
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, D-85764 Neuherberg, Germany.
Omid
O
Azimzadeh
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Research Unit Protein Science, D-80939 Munich, Germany.
Juliane
J
Merl-Pham
Radiobiology Unit, Belgian Nuclear Research Centre, SCK-CEN, B-2400 Mol, Belgium.|Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
Tine
T
Verreet
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Research Unit Protein Science, D-80939 Munich, Germany.
Stefanie M
SM
Hauck
Radiobiology Unit, Belgian Nuclear Research Centre, SCK-CEN, B-2400 Mol, Belgium.
Mohammed A
MA
Benotmane
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, D-85764 Neuherberg, Germany.|Chair of Radiation Biology, Technical University of Munich, D-80333 Munich, Germany.
Michael J
MJ
Atkinson
Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, D-85764 Neuherberg, Germany.
Soile
S
Tapio
D000818:Animals; D005260:Female; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D020543:Proteome / Q000096:biosynthesis*; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D014965:X-Rays / Q000009:adverse effects*
D009124:Muscle Proteins; D020543:Proteome