Modulation of the Chymotrypsin-Like Activity of the 20S Proteasome by Intracellular Redox Status: Effects of Glutathione Peroxidase-1 Overexpression and Antioxidant Drugs
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C. Kretz-Remy
Abstract
ATP- and ubiquitin-independent proteolysis by the 20S proteasome is responsible for the selective degradation of oxidized proteins. In vitro, the 20S proteasome shows an increased proteolytic activity toward oxidized polypeptides and the suc-LLVY-MCA peptide specific for its chymotrypsinlike activity. We have analyzed the effect of the intracellular redox status on the chymotrypsin-like activity of the 20S proteasome in human T47D cells overexpressing the detoxifiant enzyme seleno-glutathione peroxidase-1 (GPx-1). We report a 30% decreased activity of the chymotrypsin-like activity in cells overexpressing GPx-1. This phenomenon correlated with a 2-fold increase in IκBα half-life, a protein whose basal turnover is 20S proteasome-dependent. Following exposure to H2O2, these cells showed a seleno-dependently decreased accumulation of intracellular reactive oxygen species and 20S proteasome chymotrypsin like activity. Similar results were obtained in HeLa cells transiently overexpressing human GPx-1. Moreover, exposure of HeLa cells to antioxidant compounds reduced the proteasome 20S chymotrypsin like activity. In contrast, no effects were observed when HeLa cell extracts used to determine proteasome activity were incubated with either reduced or oxidized glutathione. These results suggest that GPx-1 activity or proreducing conditions can downregulate basal 20S proteasome activity. Hence, the intracellular redox status, probably through the level of oxidized proteins, is an important element that can either activate or down-regulate the 20S proteasome chymotrypsin-like activity in living cells.
Copyright © 2003 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Glutathione, Related Enzymology, and Leopold Flohé
- 'Lest I Forget Thee, Glutathione...'
- Glutathione Pathways in the Brain
- The Role of Glutathione Peroxidases in Trypanosomatids
- Cytoprotection against Oxidative Stress and the Regulation of Glutathione Synthesis
- The Parasite-Specific Trypanothione Metabolism of Trypanosoma and Leishmania
- Glutathione – Functions and Metabolism in the Malarial Parasite Plasmodium falciparum
- Oxidative Stress Caused by Inactivation of Glutathione Peroxidase and Adaptive Responses
- Versatility of Selenium Catalysis in PHGPx Unraveled by LC/ESI-MS/MS
- Modulation of the Chymotrypsin-Like Activity of the 20S Proteasome by Intracellular Redox Status: Effects of Glutathione Peroxidase-1 Overexpression and Antioxidant Drugs
- Microflora Trigger Colitis in Mice Deficient in Selenium-Dependent Glutathione Peroxidase and Induce Gpx2 Gene Expression
- Recruitment of the Interleukin-1 Receptor (IL-1RI)-Associated Kinase IRAK to the IL-1RI Is Redox Regulated
- Kinetics and Redox-Sensitive Oligomerisation Reveal Negative Subunit Cooperativity in Tryparedoxin Peroxidase of Trypanosoma brucei brucei
- Testis-Specific Expression of the Nuclear Form of Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx)
- Selective Recognition of Peptide Sequences by Glutathione Transferases: A Possible Mechanism for Modulation of Cellular Stress-Induced Signaling Pathways
- Biosynthesis of Trypanothione in Trypanosoma brucei brucei
- Transcriptional Regulation of Cytosol and Membrane Alanyl-Aminopeptidase in Human T Cell Subsets
- Regulation of Gene Transcription by a Constitutively Active Mutant of Activating Transcription Factor 2 (ATF2)
- Solvent Isotope Effect on the Reaction Catalysed by the Pyruvate Dehydrogenase Complex from Escherichia coli
- Selective Induction of Liver Parenchymal Cell Heme Oxygenase-1 in Selenium-Deficient Rats
Articles in the same Issue
- Glutathione, Related Enzymology, and Leopold Flohé
- 'Lest I Forget Thee, Glutathione...'
- Glutathione Pathways in the Brain
- The Role of Glutathione Peroxidases in Trypanosomatids
- Cytoprotection against Oxidative Stress and the Regulation of Glutathione Synthesis
- The Parasite-Specific Trypanothione Metabolism of Trypanosoma and Leishmania
- Glutathione – Functions and Metabolism in the Malarial Parasite Plasmodium falciparum
- Oxidative Stress Caused by Inactivation of Glutathione Peroxidase and Adaptive Responses
- Versatility of Selenium Catalysis in PHGPx Unraveled by LC/ESI-MS/MS
- Modulation of the Chymotrypsin-Like Activity of the 20S Proteasome by Intracellular Redox Status: Effects of Glutathione Peroxidase-1 Overexpression and Antioxidant Drugs
- Microflora Trigger Colitis in Mice Deficient in Selenium-Dependent Glutathione Peroxidase and Induce Gpx2 Gene Expression
- Recruitment of the Interleukin-1 Receptor (IL-1RI)-Associated Kinase IRAK to the IL-1RI Is Redox Regulated
- Kinetics and Redox-Sensitive Oligomerisation Reveal Negative Subunit Cooperativity in Tryparedoxin Peroxidase of Trypanosoma brucei brucei
- Testis-Specific Expression of the Nuclear Form of Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx)
- Selective Recognition of Peptide Sequences by Glutathione Transferases: A Possible Mechanism for Modulation of Cellular Stress-Induced Signaling Pathways
- Biosynthesis of Trypanothione in Trypanosoma brucei brucei
- Transcriptional Regulation of Cytosol and Membrane Alanyl-Aminopeptidase in Human T Cell Subsets
- Regulation of Gene Transcription by a Constitutively Active Mutant of Activating Transcription Factor 2 (ATF2)
- Solvent Isotope Effect on the Reaction Catalysed by the Pyruvate Dehydrogenase Complex from Escherichia coli
- Selective Induction of Liver Parenchymal Cell Heme Oxygenase-1 in Selenium-Deficient Rats
