Selenium-mediated Inhibition of Transcription Factor NF-kappa B and HIV-1 LTR Promoter Activity

Arch Toxicol. 1996;70(5):277-83. doi: 10.1007/s002040050274.

Abstract

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.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Gene Expression Regulation, Viral / drug effects
  • Gene Expression Regulation, Viral / physiology
  • Glutathione Peroxidase / metabolism
  • HIV Long Terminal Repeat / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Luciferases
  • NF-kappa B / antagonists & inhibitors*
  • Plasmids
  • Reactive Oxygen Species / metabolism
  • Selenium / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / physiology
  • Transfection

Substances

  • NF-kappa B
  • Reactive Oxygen Species
  • Glutathione Peroxidase
  • Luciferases
  • Selenium