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-kappa B and its binding to kappa B DNA sequences present in the promoter region of numerous genes. The role of selenium in NF-kappa B activation was analyzed in human T47D cells overexpressing the seleno-dependent detoxifiant enzyme glutathione peroxidase. Following exposure to H(2)O(2), these cells showed a seleno-dependent decreased accumulation of intracellular ROS and NF-kappa B activation. This phenomenon was correlated with an inhibition of the nuclear translocation of NF-kappa B (p50 subunit) and with an absence of I kappa B alpha degradation. We also report that the half-life of I kappa B 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-kappa B activation and can up-regulate I kappa B alpha normal half life.
Kretz-Remy
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CNRS-UMR 5534, Université Claude Bernard Lyon-I, Bat. Gregor Mendel, 16 rue Dubois, 69622 Villeurbanne Cédex, France.
Arrigo
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AP
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics*; D006207:Half-Life; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020672:I-kappa B Proteins; D008322:Mammals; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D012643:Selenium / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D012643:Selenium