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Int. J. Mol. Sci. 2018, 19(8), 2220; https://doi.org/10.3390/ijms19082220

The Role of the Nuclear Factor κB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation

1
German Aerospace Centre (DLR), Institute of Aerospace Medicine, Radiation Biology, Linder Höhe, D-51147 Köln, Germany
2
The Karachi Institute of Biotechnology and Genetic Engineering, University of Karachi, Karachi 75270, Sindh, Pakistan
*
Author to whom correspondence should be addressed.
Received: 30 June 2018 / Revised: 24 July 2018 / Accepted: 24 July 2018 / Published: 30 July 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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Abstract

Astronauts are exposed to considerable doses of space radiation during long-term space missions. As complete shielding of the highly energetic particles is impracticable, the cellular response to space-relevant radiation qualities has to be understood in order to develop countermeasures and to reduce radiation risk uncertainties. The transcription factor Nuclear Factor κB (NF-κB) plays a fundamental role in the immune response and in the pathogenesis of many diseases. We have previously shown that heavy ions with a linear energy transfer (LET) of 100–300 keV/µm have a nine times higher potential to activate NF-κB compared to low-LET X-rays. Here, chemical inhibitor studies using human embryonic kidney cells (HEK) showed that the DNA damage sensor Ataxia telangiectasia mutated (ATM) and the proteasome were essential for NF-κB activation in response to X-rays and heavy ions. NF-κB’s role in cellular radiation response was determined by stable knock-down of the NF-κB subunit RelA. Transfection of a RelA short-hairpin RNA plasmid resulted in higher sensitivity towards X-rays, but not towards heavy ions. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) showed that after exposure to X-rays and heavy ions, NF-κB predominantly upregulates genes involved in intercellular communication processes. This process is strictly NF-κB dependent as the response is completely absent in RelA knock-down cells. NF-κB’s role in the cellular radiation response depends on the radiation quality. View Full-Text
Keywords: nuclear factor κB; RelA; linear energy transfer; heavy ion; space mission; cytokines; chemokines; cellular radiation response nuclear factor κB; RelA; linear energy transfer; heavy ion; space mission; cytokines; chemokines; cellular radiation response
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hellweg, C.E.; Spitta, L.F.; Koch, K.; Chishti, A.A.; Henschenmacher, B.; Diegeler, S.; Konda, B.; Feles, S.; Schmitz, C.; Berger, T.; Baumstark-Khan, C. The Role of the Nuclear Factor κB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation. Int. J. Mol. Sci. 2018, 19, 2220.

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