Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells.
Nuclear factor-kappa B (NF-kappa B) regulates gene expression upon immune and inflammatory responses. It has been demonstrated that redox regulation by thiols is involved in the signal-transduction cascade. In this study, we examined the effect of glutathione (GSH) on the NF-kappa B activity and the expression of NF-kappa B subunits induced by tumor necrosis factor-alpha (TNF-alpha) using mouse vascular endothelial cells. GSH inhibited the serine phosphorylation of I kappa B-alpha by TNF-alpha, leading to the downregulation of NF-kappa B-DNA binding activity followed by decreased expression of p65/p50 and I kappa B mRNAs. The regulation of the autoregulatory loop for the NF-kappa B activation and the expression of NF-kappa B subunits may be important in endothelial cells in response to cytokines.
Cho
S
S
Department of Biochemistry and Molecular Biology in Disease, Nagasaki University School of Medicine, Japan.
Urata
Y
Y
Iida
T
T
Goto
S
S
Yamaguchi
M
M
Sumikawa
K
K
Kondo
T
T
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000502:physiology*; D006390:Hemangioendothelioma; D020672:I-kappa B Proteins; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D005978:Glutathione