Quantitative proteomic analysis reveals induction of premature senescence in human umbilical vein endothelial cells exposed to chronic low-dose rate gamma radiation

Authors

  • Ramesh Yentrapalli,

    1. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany
    2. Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
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  • Omid Azimzadeh,

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

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

    1. Helmholtz Zentrum München, German Research Center for Environmental Health, Department of Protein Science, Proteomics Core Facility, Neuherberg, Germany
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  • Andrzej Wojcik,

    1. Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
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  • Mats Harms-Ringdahl,

    1. Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
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  • Michael J. Atkinson,

    1. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany
    2. Department of Radiation Oncology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
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  • Siamak Haghdoost,

    1. Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden
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  • Soile Tapio

    Corresponding author
    • Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany
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Correspondence: Dr. Soile Tapio, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany

E-mail: soile.tapio@helmholtz-muenchen.de

Fax: +49 (0)89-3187-3378

Abstract

Chronic low-dose ionizing radiation induces cardiovascular disease in human populations but the mechanism is largely unknown. We suggested that chronic radiation exposure may induce endothelial cell senescence that is associated with vascular damage in vivo. We investigated whether chronic radiation exposure is causing a change in the onset of senescence in endothelial cells in vitro. Indeed, when exposed to continuous low-dose rate gamma radiation (4.1 mGy/h), primary human umbilical vein endothelial cells (HUVECs) initiated senescence much earlier than the nonirradiated control cells. We investigated the changes in the protein expression of HUVECs before and during the onset of radiation-induced senescence. Cellular proteins were quantified using isotope-coded protein label technology after 1, 3, and 6 weeks of radiation exposure. Several senescence-related biological pathways were influenced by radiation, including cytoskeletal organization, cell–cell communication and adhesion, and inflammation. Immunoblot analysis showed an activation of the p53/p21 pathway corresponding to the progressing senescence. Our data suggest that chronic radiation-induced DNA damage and oxidative stress result in induction of p53/p21 pathway that inhibits the replicative potential of HUVECs and leads to premature senescence. This study contributes to the understanding of the increased risk of cardiovascular diseases seen in populations exposed to chronic low-dose irradiation.

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