Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms19082220
Keywords
nuclear factor B; RelA; linear energy transfer; heavy ion; space mission; cytokines; chemokines; cellular radiation response
Funding
- DLR grant FuE-Projekt ISS LIFE (programm RF-FuW, Teilprogramm) [475]
- Helmholtz Association
- German Aerospace Center [VH-KO-300]
- European Union (EURONS)
- International Open Laboratory of the National Institute of Radiation Science (NIRS)
- National Institutes for Quantum and Radiological Science and Technology (QST), Anagawa, Inageku, in Chiba, Japan
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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 B (NF-B) 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/mu m have a nine times higher potential to activate NF-B 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-B activation in response to X-rays and heavy ions. NF-B's role in cellular radiation response was determined by stable knock-down of the NF-B 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-B predominantly upregulates genes involved in intercellular communication processes. This process is strictly NF-B dependent as the response is completely absent in RelA knock-down cells. NF-B's role in the cellular radiation response depends on the radiation quality.
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