Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation
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|
|HGF - Program:||Space|
|HGF - Program Themes:||W FR - Forschung unter Weltraumbedingungen|
|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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