Selenium: A key element that controls NF-kappa B activation and I kappa B alpha half life

Treatment of mammalian cells with hydrogen peroxide induces the nuclear translocation of the transcription factor NF-kappaB and its binding to kappaB DNA sequences present in the promoter region of numerous genes. The role of selenium in NF-kappaB activation was analyzed in human T47D cells overexpressing the seleno-dependent detoxifiant enzyme glutathione peroxidase. Following exposure to H2O2, these cells showed a seleno-dependent decreased accumulation of intracellular ROS and NF-kappaB activation. This phenomenon was correlated with an inhibition of the nuclear translocation of NF-kappaB (p50 subunit) and with an absence of I kappaB alpha degradation. We also report that the half-life of I kappaB alpha 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-kappaB activation and can up-regulate I kappaB alpha normal half life.