Effects of antioxidant enzyme modulations on interleukin-1-induced nuclear factor kappa B activation.
Nuclear factor kappa B (NF-kappa B) is a potent and pleiotropic transcription factor that can be activated by a wide variety of inducers, including interleukin-1 (IL-1). Although the detailed activation mechanism of NF-kappa B is still under investigation, it requires both phosphorylation and degradation of its inhibitory subunit I kappa B and the presence of an oxidative environment. In this study, we systematically evaluated the influence of glutathione peroxidase, glutathione reductase and catalase on IL-1-induced NF-kappa B activation by analysing the effect of specific inhibitors of these enzymes. For the three antioxidant enzymes mentioned, their inhibition correlated with an overactivation of NF-kappa B, particularly for glutathione peroxidase. Inversely, we tested the response of glutathione peroxidase-transfected cells on NF-kappa B activation, which was lower as compared with the parental cells. Furthermore, interleukin-6 production also correlated perfectly with the reduced level of NF-kappa B activation is these experiments. The results clearly show that NF-kappa B activation is, strongly dependent on the antioxidant potential of the cells, especially on the activity of reduced glutathione-dependent enzymes such as glutathione peroxidase. The results support the hypothesis that the level of the oxidised glutathione:reduced glutathione ratio and the activity of intracellular antioxidant enzymes play a major role in NF-kappa B tine tuning.
Renard
P
P
Laboratoire de Biochimie Cellulaire, Facultés Universitaires, Namur, Belgium.
Zachary
M D
MD
Bougelet
C
C
Mirault
M E
ME
Haegeman
G
G
Remacle
J
J
Raes
M
M
D000640:Amitrole / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002374:Catalase / Q000502:physiology*; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000502:physiology*; D005980:Glutathione Reductase / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*
D007375:Interleukin-1; D016328:NF-kappa B; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D002330:Carmustine; D000640:Amitrole