Hellweg, Christine E. and Langen, Britta and Klimow, Galina and Ruscher, Roland and Schmitz, Claudia and Baumstark-Khan, Christa and Reitz, Guenther (2009) Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation. Advances in Space Research, 44, pp. 907-916. Elsevier. DOI: 10.1016/j.asr.2009.07.009.
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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 κB (NF-κB) 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-κB-dependent gene induction (HEK-pNF-κB-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-κB inhibitors can map functional details of the NF-κB pathway and the influence of radiation-induced NF-κB activation on various cellular outcomes such as survival or cell cycle arrest. In this work, the efficacy and cytotoxicity of four different NF-κB inhibitors, caffeic acid phenethyl ester (CAPE), capsaicin, the proteasome inhibitor MG-132, and the cell permeable peptide NF-κB SN50 were analyzed using HEK-pNF-κB-d2EGFP/Neo cells. In the recommended concentration range, only CAPE displayed considerable cytotoxicity. CAPE and capsaicin partially inhibited NF-κB activation by the cytokine tumor necrosis factor α. MG-132 completely abolished the activation and was therefore used for experiments with X-rays. NF-κB SN-50 could not reduce NF-κB dependent expression of the reporter destabilized Enhanced Green Fluorescent Protein (d2EGFP). MG-132 entirely suppressed the X-ray induced NF-κB activation in HEK-pNF-κB-d2EGFP/Neo cells. In conclusion, the degradation of the inhibitor of NF-κB (IκB) in the proteasome is essential for X-ray induced NF-κB activation, and MG-132 will be useful in studies of the NF-κB pathway involvement in the cellular response to heavy ion exposure and other space-relevant radiation qualities.
|Title:||Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation|
|Journal or Publication Title:||Advances in Space Research|
|In ISI Web of Science:||Yes|
|Page Range:||pp. 907-916|
|Keywords:||Nuclear factor κB inhibitors; Ionizing radiation; Human cells; Proteasome; Capsaicin; Caffeic acid phenethyl ester|
|HGF - Research field:||Aeronautics, Space and Transport (old)|
|HGF - Program:||Space (old)|
|HGF - Program Themes:||W FR - Forschung unter Weltraumbedingungen (old)|
|DLR - Research area:||Space|
|DLR - Program:||W FR - Forschung unter Weltraumbedingungen|
|DLR - Research theme (Project):||W - Vorhaben Strahlenbiologie (old)|
|Institutes and Institutions:||Institute of Aerospace Medicine > Radiation Biology|
|Deposited By:||Kerstin Kopp|
|Deposited On:||05 Nov 2009 11:21|
|Last Modified:||20 Mar 2013 19:42|
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