The Inhibition of NF-B Activation Pathways and the Induction of Apoptosis by Dithiocarbamates in T Cells Are Blocked by the Glutathione Precursor N-Acetyl-L-Cysteine
-
Paula C. Fernandez
Abstract
Nuclear factor-κB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-κB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and combined, on different stages of the NF-κB activation pathway, in primary and in transformed T cells. We show that NAC, contrary to its reported role as an NF-κB inhibitor, can actually enhance rather than inhibit IκB degradation and, most importantly, show that in all cases NAC exerts a dominant antagonistic effect on PDTC-mediated NF-κB inhibition. This was observed at the level of IκB degradation, NF-κB DNA binding, and HIV-LTR-driven reporter gene expression. NAC also counteracted growth arrest and apoptosis induced by dithiocarbamates. Antagonistic effects were further observed at the level of jun-NH2-terminal kinase, p38 and ATF-2 activation. Our findings argue against the widely accepted assumption that NAC inhibits all NF-κB activation pathways and shows that two compounds, previously thought to function through a common inhibitory mechanism, can also have antagonistic effects.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
Artikel in diesem Heft
- To Our Authors, Readers and Subscribers
- Editor's Note
- A Chimpanzee Millennium
- Molecular Genetics of Dopa-Responsive Dystonia
- In Vitro Transcription of a TATA-Less Promoter: Negative Regulation by the Not1 Protein
- Fast Control of DNA Replication in Response to Hypoxia and to Inhibited Protein Synthesis in CCRF-CEM and HeLa Cells
- The Inhibition of NF-B Activation Pathways and the Induction of Apoptosis by Dithiocarbamates in T Cells Are Blocked by the Glutathione Precursor N-Acetyl-L-Cysteine
- Xylose Utilisation: Cloning and Characterisation of the Xylose Reductase from Candida tenuis
- Xylose Utilisation: Cloning and Characterisation of the Xylitol Dehydrogenase from Galactocandida mastotermitis
- Thermodynamic Properties and DNA Binding of the ParD Protein from the Broad Host-Range Plasmid RK2/RP4 Killing System
- Dipeptidyl Peptidase III from Rat Liver Cytosol: Purification, Molecular Cloning and Immunohistochemical Localization
- Genomic Expansion Across the Albumin Gene Family on Human Chromosome 4q Is Directional
- Comparison of the Tamoxifen Regulated Chimeric Cre Recombinases MerCreMer and CreMer
- The Human Cathepsin F Gene a Fusion Product between an Ancestral Cathepsin and Cystatin Gene
- Characterization of a New Member of the TNF Family Expressed on Antigen Presenting Cells
- Vascular Endothelial Growth Factor (VEGF) and Its Receptors in Tumor-Bearing Dogs
- Molecular Cloning and Characterization of a cDNA Encoding a Transferrin Homolog from Bombyx mori
- Mitochondria-Derived and Extra-Mitochondrial Human Type-1 Porin Are Identical as Revealed by Amino Acid Sequencing and Electrophysiological Characterisation
- Acknowledgement
- Content Index
- Author Index
- Subject Index
Artikel in diesem Heft
- To Our Authors, Readers and Subscribers
- Editor's Note
- A Chimpanzee Millennium
- Molecular Genetics of Dopa-Responsive Dystonia
- In Vitro Transcription of a TATA-Less Promoter: Negative Regulation by the Not1 Protein
- Fast Control of DNA Replication in Response to Hypoxia and to Inhibited Protein Synthesis in CCRF-CEM and HeLa Cells
- The Inhibition of NF-B Activation Pathways and the Induction of Apoptosis by Dithiocarbamates in T Cells Are Blocked by the Glutathione Precursor N-Acetyl-L-Cysteine
- Xylose Utilisation: Cloning and Characterisation of the Xylose Reductase from Candida tenuis
- Xylose Utilisation: Cloning and Characterisation of the Xylitol Dehydrogenase from Galactocandida mastotermitis
- Thermodynamic Properties and DNA Binding of the ParD Protein from the Broad Host-Range Plasmid RK2/RP4 Killing System
- Dipeptidyl Peptidase III from Rat Liver Cytosol: Purification, Molecular Cloning and Immunohistochemical Localization
- Genomic Expansion Across the Albumin Gene Family on Human Chromosome 4q Is Directional
- Comparison of the Tamoxifen Regulated Chimeric Cre Recombinases MerCreMer and CreMer
- The Human Cathepsin F Gene a Fusion Product between an Ancestral Cathepsin and Cystatin Gene
- Characterization of a New Member of the TNF Family Expressed on Antigen Presenting Cells
- Vascular Endothelial Growth Factor (VEGF) and Its Receptors in Tumor-Bearing Dogs
- Molecular Cloning and Characterization of a cDNA Encoding a Transferrin Homolog from Bombyx mori
- Mitochondria-Derived and Extra-Mitochondrial Human Type-1 Porin Are Identical as Revealed by Amino Acid Sequencing and Electrophysiological Characterisation
- Acknowledgement
- Content Index
- Author Index
- Subject Index
