Selenium-mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity.
The eukaryotic transcription factor NF-kappa B is involved in the inducible expression of various inflammatory genes as well as in HIV-1 replication. Activation of NF-kappa B is induced by prooxidants and several stimuli eliciting oxidative stress, such as cytokines, lipopolysaccharide, UV irradiation and other mediators. Various antioxidants inhibit NF-kappa B activation in response to these stimuli. In this study, we have investigated the effects of selenium, an integral component of glutathione peroxidase (GPX), on NF-kappa B activation. In selenium-deprived Jurkat and ESb-L T lymphocytes, supplementation of selenium led to a substantial increase of GPX activity. Analysis of DNA binding revealed that NF-kappa B activation in response to TNF was significantly inhibited under these conditions. Likewise, reporter gene assays using luciferase constructs driven by the HIV-1 long terminal repeat showed a dose-dependent inhibition of NF-kappa B controlled gene expression by selenium. The effects of selenium were specific for NF-kappa B, since the activity of the transcription factor AP-1 was not suppressed. These data suggest that selenium supplementation may be used to modulate the expression of NF-kappa B target genes and HIV-1.
Makropoulos
V
V
Zentrum Arbeit und Gesundheit Dortmund/Wuppertal, Universität Dortmund, Germany.
Brüning
T
T
Schulze-Osthoff
K
K
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D005979:Glutathione Peroxidase / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008156:Luciferases; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D014162:Transfection
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D008156:Luciferases; D012643:Selenium