Up-stream events in the nuclear factor jB activation cascade in response to sparsely ionizing radiation

Hellweg, Christine E., Langen, Britta, Klimow, Galina, Ruscher, Roland, Schmitz, Claudia, Baumstark-Khan, Christa, and Reitz, Günther (2009) Up-stream events in the nuclear factor jB activation cascade in response to sparsely ionizing radiation. Advances In Space Research, 44 (8). pp. 907-916.

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Radiation is a potentially limiting factor for manned long-term space missions. Prolonged exposure to galactic cosmic rays may shorten the healthy life-span after return to Earth due to cancer induction. During the mission, a solar flare can be life threatening. For better risk estimation and development of appropriate countermeasures, the study of the cellular radiation response is necessary. Since apoptosis may be a mechanism the body uses to eliminate damaged cells, the induction by cosmic radiation of the nuclear antiapoptotic transcription factor nuclear factor jB (NF-jB) could influence the cancer risk of astronauts exposed to cosmic radiation by improving the survival of radiation-damaged cells. In previous studies using a screening assay for the detection of NF-jB-dependent gene induction (HEK-pNF-jB-d2EGFP/Neo cells), the activation of this transcription factor by heavy ions was shown [Baumstark-Khan, C., Hellweg, C.E., Arenz, A., Meier, M.M. Cellular monitoring of the nuclear factor kappa B pathway for assessment of space environmental radiation. Radiat. Res. 164, 527–530, 2005]. Studies with NF-jB inhibitors can map functional details of the NF-jB pathway and the influence of radiation-induced NF-jB activation on various cellular outcomes such as survival or cell cycle arrest. In this work, the efficacy and cytotoxicity of four different NF-jB inhibitors, caffeic acid phenethyl ester (CAPE), capsaicin, the proteasome inhibitor MG-132, and the cell permeable peptide NF-jB SN50 were analyzed using HEK-pNF-jB-d2EGFP/Neo cells. In the recommended concentration range, only CAPE displayed considerable cytotoxicity. CAPE and capsaicin partially inhibited NF-jB activation by the cytokine tumor necrosis factor a. MG-132 completely abolished the activation and was therefore used for experiments with X-rays. NF-jB SN-50 could not reduce NF-jB dependent expression of the reporter destabilized Enhanced Green Fluorescent Protein (d2EGFP). MG-132 entirely suppressed the X-ray induced NF-jB activation in HEK-pNF-jB-d2EGFP/Neo cells. In conclusion, the degradation of the inhibitor of NF-jB (IjB) in the proteasome is essential for X-ray induced NF-jB activation, and MG-132 will be useful in studies of the NF-jB pathway involvement in the cellular response to heavy ion exposure and other space-relevant radiation qualities.

Item ID: 60663
Item Type: Article (Research - C1)
ISSN: 1879-1948
Keywords: Nuclear factor κB inhibitors; Ionizing radiation; Human cells; Proteasome; Capsaicin; Caffeic acid; phenethyl ester
Copyright Information: © 2009 COSPAR. Published by Elsevier Ltd. All rights reserved.
Date Deposited: 17 Feb 2020 01:28
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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