In-Utero Low-Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome

• Published in: PloS one Vol. 11; no. 6; p. e0156952
• Main Authors: Bakshi, Mayur V, Azimzadeh, Omid, Merl-Pham, Juliane, Verreet, Tine, Hauck, Stefanie M, Benotmane, Mohammed A, Atkinson, Michael J, Tapio, Soile
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.06.2016; Public Library of Science (PLoS)
• Subjects: Animals; Antiviral agents; Atherosclerosis; Bioinformatics; Biology; Biology and Life Sciences; Cardiomyopathy; Cardiovascular disease; Cardiovascular diseases; Cytoskeleton; Data processing; Embryogenesis; Embryonic development; Embryonic growth stage; Environmental health; Exposure; Female; Females; Fetuses; Heart; Heart diseases; Heat shock; Immunoblotting; Ionizing radiation; Irradiation; Kinases; Laboratories; Light; Male; Mass spectrometry; Mass spectroscopy; Maternal Exposure - adverse effects; Medicine and Health Sciences; Mice; Mitochondria; Molecular chains; Molecular modelling; Muscle Proteins - biosynthesis; Myocardium - metabolism; Neurosciences; Nuclear physics; Offspring; Oxygen; Physical Sciences; Physiological aspects; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - metabolism; Proteins; Proteome - biosynthesis; Proteomics; Radiation; Radiation dosage; Radiation effects; Radiation Injuries, Experimental - metabolism; Reactive oxygen species; Research and Analysis Methods; Risk factors; X-Rays - adverse effects; Belgium; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156952

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.