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

Mayur V Bakshi; Omid Azimzadee"h; Juliane Merl-Pham; Tine Verreet; Stefanie M Hauck; Rafi Benotmane; Michael J Atkinson; Soile Tapio; Sarah Baatout

doi:10.1371/journal.pone.0156952

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

Mayur V Bakshi, Omid Azimzadee"h, Juliane Merl-Pham, Tine Verreet, Stefanie M Hauck, Rafi Benotmane, Michael J Atkinson, Soile Tapio, Sarah Baatout

Research output › peer-review

Abstract

Prenatal exposure to stress such as increased level of reactive oxygen species or antiviraltherapy are known factors leading to adult heart defects. The risks following a radiationexposure during fetal period are unknown, as are the mechanisms of any potential cardiacdamage. The aim of this study was to gather evidence for possible damage by investigatinglong-term changes in the mouse heart proteome after prenatal exposure to low and moderateradiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a singletotal body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring weresacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissuewas performed using Isotope Coded Protein Label technology and tandem mass spectrometry.The proteomics data were analyzed by bioinformatics and key changes were validatedby immunoblotting. Persistent changes were observed in the expression of proteins representingmitochondrial 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 kinaseMAP4K4 that is essential for the embryonic development of mouse heart was

Original language	English
Number of pages	14
Journal	PLOS ONE
Volume	11
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0156952
State	Published - 8 Jun 2016

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title = "In Utero Low Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome",

abstract = "Prenatal exposure to stress such as increased level of reactive oxygen species or antiviraltherapy are known factors leading to adult heart defects. The risks following a radiationexposure during fetal period are unknown, as are the mechanisms of any potential cardiacdamage. The aim of this study was to gather evidence for possible damage by investigatinglong-term changes in the mouse heart proteome after prenatal exposure to low and moderateradiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a singletotal body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring weresacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissuewas performed using Isotope Coded Protein Label technology and tandem mass spectrometry.The proteomics data were analyzed by bioinformatics and key changes were validatedby immunoblotting. Persistent changes were observed in the expression of proteins representingmitochondrial 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 kinaseMAP4K4 that is essential for the embryonic development of mouse heart was ",

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AU - Verreet, Tine

AU - Hauck, Stefanie M

AU - Benotmane, Rafi

AU - Atkinson, Michael J

AU - Tapio, Soile

A2 - Baatout, Sarah

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N2 - Prenatal exposure to stress such as increased level of reactive oxygen species or antiviraltherapy are known factors leading to adult heart defects. The risks following a radiationexposure during fetal period are unknown, as are the mechanisms of any potential cardiacdamage. The aim of this study was to gather evidence for possible damage by investigatinglong-term changes in the mouse heart proteome after prenatal exposure to low and moderateradiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a singletotal body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring weresacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissuewas performed using Isotope Coded Protein Label technology and tandem mass spectrometry.The proteomics data were analyzed by bioinformatics and key changes were validatedby immunoblotting. Persistent changes were observed in the expression of proteins representingmitochondrial 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 kinaseMAP4K4 that is essential for the embryonic development of mouse heart was

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