Inhibition of NF-κB Activation in Human T-Cell Lines by Anetholdithiolthione

Nuclear factor (NF)-κB is a redox sensitive cytosolic transcription factor. Redox regulation of NF-κB has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-κB activation may be an effective strategy for acquired immunodeficiency syndrome therap...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1996-01, Vol.218 (1), p.148-153
Main Authors: Sen, Chandan K., Traber, Katrina E., Packer, Lester
Format: Article
Language:English
Subjects:
Anethole Trithione - pharmacology
Cell Line
Cell Nucleus - metabolism
Humans
Hydrogen Peroxide - pharmacology
Kinetics
Lymphoma, T-Cell
NF-kappa B - antagonists & inhibitors
NF-kappa B - isolation & purification
NF-kappa B - metabolism
T-Lymphocytes
Tetradecanoylphorbol Acetate - pharmacology
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Nuclear factor (NF)-κB is a redox sensitive cytosolic transcription factor. Redox regulation of NF-κB has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-κB activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-κB activation in response to a variety of stimuli such as H2O2, phorbol myrisitate acetate (PMA) or tumor necrosis factor α (TNFα). PMA and TNFα induced activation of (NF)-κB in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-κB activation.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1996.0026