Selenium: A key element that controls NF-κB activation and IκBα half life

Article type: Research Article

Authors: Kretz-Remy, Carole | Arrigo, André-Patrick

Affiliations: CNRS-UMR 5534, Université Claude Bernard Lyon-I, Bat. Gregor Mendel, 16 rue Dubois, 69622 Villeurbanne Cédex, France

Note: [] Equipe Stress oxydant, chaperon et apoptose, CNRS-UMR 5534, Université Claude Bernard Lyon I, 43 Boulevard du 11 Novembre, F-69622 Villeurbanne Cédex, France. Tel.: +33 47244 8595; Fax: +33 47244 0555; E-mail: [email protected]

Abstract: Treatment of mammalian cells with hydrogen peroxide induces the nuclear translocation of the transcription factor NF-κB and its binding to κB DNA sequences present in the promoter region of numerous genes. The role of selenium in NF-κB activation was analyzed in human T47D cells overexpressing the seleno-dependent detoxifiant enzyme glutathione peroxidase. Following exposure to H_2O_2, these cells showed a seleno-dependent decreased accumulation of intracellular ROS and NF-κB activation. This phenomenon was correlated with an inhibition of the nuclear translocation of NF-κB (p50 subunit) and with an absence of IκBα degradation. We also report that the half-life of IκBα in untreated cells was increased two-fold by the overexpression of active glutathione peroxidase. These results suggest that selenium is a key element that through its modulation of glutathione peroxidase activity can inhibit NF-κB activation and can up-regulate IκBα normal half life.

Keywords: selenium, glutathione peroxidase, redox regulation, NF-κB, IκB

Journal: BioFactors, vol. 14, no. 1-4, pp. 117-125, 2001