Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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DNA / metabolism
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Down-Regulation / drug effects
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Down-Regulation / physiology*
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism*
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Glutathione / physiology*
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Hemangioendothelioma
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I-kappa B Proteins
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Mice
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / biosynthesis
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NF-kappa B / genetics
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NF-kappa B / physiology*
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NF-kappa B p50 Subunit
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Phosphorylation / drug effects
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Protein Binding / drug effects
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Transcription Factor RelA
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / physiology*
Substances
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DNA-Binding Proteins
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I-kappa B Proteins
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NF-kappa B
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NF-kappa B p50 Subunit
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Nfkbia protein, mouse
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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DNA
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Glutathione