Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression
| Autor: | Salvatore Salzano, Matilde Valeria Ursini, Francesca Salvemini, Angela Iervolino, Stefania Filosa, Annamaria Franzè |
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| Přispěvatelé: | Salvemini, F., Franzè, Annamaria., Iervolino, A., Filosa, S., Salzano, S., Ursini, M. V. |
| Rok vydání: | 1999 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities GPX1 Pyrrolidines Glutathione reductase Glucosephosphate Dehydrogenase Pentose phosphate pathway Biology Biochemistry Antioxidants chemistry.chemical_compound Thiocarbamates hemic and lymphatic diseases parasitic diseases Tumor Cells Cultured Humans Glucose-6-phosphate dehydrogenase Buthionine Sulfoximine Molecular Biology Diamide chemistry.chemical_classification Glutathione Peroxidase Glutathione peroxidase nutritional and metabolic diseases Cell Biology Glutathione Catalase Flow Cytometry Glutathione Reductase Cell killing chemistry Reactive Oxygen Species Intracellular HeLa Cells |
| Zdroj: | The Journal of biological chemistry 274 (1999): 2750–2757. info:cnr-pdr/source/autori:Salvemini F, Franzé A, Iervolino A, Filosa S, Salzano S, Ursini MV./titolo:Enhanced glutathione levels and oxidoresistance mediated by increased glucose-6-phosphate dehydrogenase expression./doi:/rivista:The Journal of biological chemistry (Print)/anno:1999/pagina_da:2750/pagina_a:2757/intervallo_pagine:2750–2757/volume:274 274 (1999): 2750–2757. doi:10.1074/jbc.274.5.2750 info:cnr-pdr/source/autori:SALVEMINI F, FRANZE A, IERVOLINO A, FILOSA S, SALZANO S, URSINI MV/titolo:Enhanced glutathione levels oxidoresistance mediated by increased glucose-6-phosphate dehydrogenase expression/doi:10.1074%2Fjbc.274.5.2750/rivista:The Journal of biological chemistry (Print)/anno:1999/pagina_da:2750/pagina_a:2757/intervallo_pagine:2750–2757/volume:274 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.5.2750 |
| Popis: | Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway that is responsible for the generation of NADPH, which is required in many detoxifying reactions. We have recently demonstrated that G6PD expression is induced by a variety of chemical agents acting at different steps in the biochemical pathway controlling the intracellular redox status. Although we obtained evidence that the oxidative stress-mediated enhancement of G6PD expression is a general phenomenon, the functional significance of such G6PD induction after oxidant insult is still poorly understood. In this report, we used a GSH-depleting drug that determines a marked decrease in the intracellular pool of reduced glutathione and a gradual but notable increase in G6PD expression. Both effects are seen soon after drug addition. Once G6PD activity has reached the maximum, the GSH pool is restored. We suggest and also provide the first direct evidence that G6PD induction serves to maintain and regenerate the intracellular GSH pool. We used HeLa cell clones stably transfected with the human G6PD gene that display higher G6PD activity than the parent HeLa cells. Although the activities of glutathione peroxidase, glutathione reductase, and catalase were comparable in all strains, the concentrations of GSH were significantly higher in G6PD-overexpressing clones. A direct consequence of GSH increase in these cells is a decreased reactive oxygen species production, which makes these cells less sensitive to the oxidative burst produced by external stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong protection against oxidants-mediated cell killing. We also observe that NF-kappa B activation, in response to tumor necrosis factor-alpha treatment, is strongly reduced in human HeLa cells overexpressing G6PD. |
| Databáze: | OpenAIRE |
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