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

Hellweg, Christine E. und Langen, Britta und Klimow, Galina und Ruscher, Roland und Schmitz, Claudia und Baumstark-Khan, Christa und Reitz, Guenther (2009) Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation. Advances in Space Research, 44, Seiten 907-916. Elsevier. DOI: 10.1016/j.asr.2009.07.009.

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Kurzfassung

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.

Dokumentart:Zeitschriftenbeitrag
Titel:Up-stream events in the nuclear factor κB activation cascade in response to sparsely ionizing radiation
Autoren:
AutorenInstitution oder E-Mail-Adresse der Autoren
Hellweg, Christine E.NICHT SPEZIFIZIERT
Langen, Britta NICHT SPEZIFIZIERT
Klimow, Galina NICHT SPEZIFIZIERT
Ruscher, Roland NICHT SPEZIFIZIERT
Schmitz, Claudia NICHT SPEZIFIZIERT
Baumstark-Khan, Christa NICHT SPEZIFIZIERT
Reitz, Guenther NICHT SPEZIFIZIERT
Datum:2009
Erschienen in:Advances in Space Research
Referierte Publikation:Ja
In SCOPUS:Ja
In ISI Web of Science:Ja
Band:44
DOI :10.1016/j.asr.2009.07.009
Seitenbereich:Seiten 907-916
Herausgeber:
HerausgeberInstitution und/oder E-Mail-Adresse der Herausgeber
Cospar, Publ.NICHT SPEZIFIZIERT
Verlag:Elsevier
Status:veröffentlicht
Stichwörter:Nuclear factor κB inhibitors; Ionizing radiation; Human cells; Proteasome; Capsaicin; Caffeic acid phenethyl ester
HGF - Forschungsbereich:Verkehr und Weltraum (alt)
HGF - Programm:Weltraum (alt)
HGF - Programmthema:W FR - Forschung unter Weltraumbedingungen (alt)
DLR - Schwerpunkt:Weltraum
DLR - Forschungsgebiet:W FR - Forschung unter Weltraumbedingungen
DLR - Teilgebiet (Projekt, Vorhaben):W - Vorhaben Strahlenbiologie (alt)
Standort: Köln-Porz
Institute & Einrichtungen:Institut für Luft- und Raumfahrtmedizin > Strahlenbiologie
Hinterlegt von: Kerstin Kopp
Hinterlegt am:05 Nov 2009 11:21
Letzte Änderung:20 Mär 2013 19:42

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