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Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

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NB-Photonics
Abstract
Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/mu m) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappa B, may be involved in these cellular responses.
Keywords
cardiovascular system, high-linear energy transfer, endothelial cells, DOSE RADIATION-THERAPY, DNA-DAMAGE, KAPPA-B, CYTOSKELETON, ACTIVATION, MECHANISMS, CYTOMETRY, HELICASE, ADHESION, DISEASES, radiation, gene expression

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Citation

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Chicago
Beck, Michaël, Charlotte Rombouts, Marjan Moreels, An Aerts, Roel Quintens, Kevin Tabury, Arlette Michaux, et al. 2014. “Modulation of Gene Expression in Endothelial Cells in Response to High LET Nickel Ion Irradiation.” International Journal of Molecular Medicine 34 (4): 1124–1132.
APA
Beck, Michaël, Rombouts, C., Moreels, M., Aerts, A., Quintens, R., Tabury, K., Michaux, A., et al. (2014). Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 34(4), 1124–1132.
Vancouver
1.
Beck M, Rombouts C, Moreels M, Aerts A, Quintens R, Tabury K, et al. Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE. 2014;34(4):1124–32.
MLA
Beck, Michaël, Charlotte Rombouts, Marjan Moreels, et al. “Modulation of Gene Expression in Endothelial Cells in Response to High LET Nickel Ion Irradiation.” INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34.4 (2014): 1124–1132. Print.
@article{5751279,
  abstract     = {Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/mu m) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappa B, may be involved in these cellular responses.},
  author       = {Beck, Micha{\"e}l and Rombouts, Charlotte and Moreels, Marjan and Aerts, An and Quintens, Roel and Tabury, Kevin and Michaux, Arlette and Janssen, Ann and Neefs, Mieke and Ernst, Eric and Dieriks, Birger and Lee, Ryonfa and De Vos, Winnok and Lambert, Charles and Van Oostveldt, Patric and Baatout, Sarah},
  issn         = {1107-3756},
  journal      = {INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE},
  keyword      = {cardiovascular system,high-linear energy transfer,endothelial cells,DOSE RADIATION-THERAPY,DNA-DAMAGE,KAPPA-B,CYTOSKELETON,ACTIVATION,MECHANISMS,CYTOMETRY,HELICASE,ADHESION,DISEASES,radiation,gene expression},
  language     = {eng},
  number       = {4},
  pages        = {1124--1132},
  title        = {Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation},
  url          = {http://dx.doi.org/10.3892/ijmm.2014.1893},
  volume       = {34},
  year         = {2014},
}

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