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Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study

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Abstract

Epidemiological studies establish that children and young adults are especially susceptible to radiation-induced cardiovascular disease (CVD). The biological mechanisms behind the elevated CVD risk following exposure at young age remain unknown. The present study aims to elucidate the long-term effects of ionizing radiation by studying the murine cardiac proteome after exposure to low and moderate radiation doses. NMRI mice received single doses of total body 60Co gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes in cardiac protein expression were quantified using isotope-coded protein label and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The four doses shared 9 deregulated proteins. Bioinformatics analysis showed that most of the deregulated proteins belonged to a limited set of biological categories, including metabolic processes, inflammatory response, and cytoskeletal structure. The transcription factor peroxisome proliferator-activated receptor alpha was predicted as a common upstream regulator of several deregulated proteins. This study indicates that both adaptive and maladaptive responses to the initial radiation damage persist well into adulthood. It will contribute to the understanding of the long-term consequences of radiation-induced injury and developmental alterations in the neonatal heart.

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Abbreviations

Gy:

Gray

IPA:

Ingenuity Pathway Analysis

CVD:

Cardiovascular disease

H/L:

Heavy to light ratio

ICPL:

Isotope-coded protein label

LC–MS:

Liquid chromatography mass spectrometry

PND:

Postnatal day

TBI:

Total body irradiation

PPAR:

Peroxisome proliferator-activated receptor

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Acknowledgments

The research leading to these results is supported by a grant from the European Community’s Seventh Framework Program (EURATOM) Contract No. 295823 (PROCARDIO) and Contract No. 295552 (CEREBRAD). We thank Stefanie Winkler for her technical assistance.

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Authors and Affiliations

  1. Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany

    Mayur V. Bakshi, Zarko Barjaktarovic, Omid Azimzadeh, Stefan J. Kempf, Michael J. Atkinson & Soile Tapio

  2. Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany

    Juliane Merl & Stefanie M. Hauck

  3. Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden

    Per Eriksson & Sonja Buratovic

  4. Department of Radiation Oncology, Klinikum Recht der Isar, Technical University of Munich, Munich, Germany

    Michael J. Atkinson

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  1. Mayur V. Bakshi
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  2. Zarko Barjaktarovic
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  3. Omid Azimzadeh
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  4. Stefan J. Kempf
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  5. Juliane Merl
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  6. Stefanie M. Hauck
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  8. Sonja Buratovic
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  9. Michael J. Atkinson
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  10. Soile Tapio
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Correspondence to Soile Tapio.

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Bakshi, M.V., Barjaktarovic, Z., Azimzadeh, O. et al. Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study. Radiat Environ Biophys 52, 451–461 (2013). https://doi.org/10.1007/s00411-013-0483-8

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