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

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 ?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/µm 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.

SUBMITTER: Hellweg CE 

PROVIDER: S-EPMC6121395 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature