Glutathione Levels and Sensitivity to Apoptosis Are Regulated by Changes in Transaldolase Expression
| Autor: | Eliza Hutter, Nick J. Gonchoroff, Emanuela Colombo, Andras Perl, Katalin Banki |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Programmed cell death
T-Lymphocytes Apoptosis Cell Biology Glutathione Glucosephosphate Dehydrogenase Biology Pentose phosphate pathway Biochemistry Jurkat cells Molecular biology Transaldolase Pentose Phosphate Pathway Nordihydroguaiaretic acid chemistry.chemical_compound chemistry Tumor Cells Cultured Humans Buthionine sulfoximine fas Receptor Reactive Oxygen Species Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 271:32994-33001 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.51.32994 |
| Popis: | Transaldolase (TAL) is a key enzyme of the reversible nonoxidative branch of the pentose phosphate pathway (PPP) that is responsible for the generation of NADPH to maintain glutathione at a reduced state (GSH) and, thus, to protect cellular integrity from reactive oxygen intermediates (ROIs). Formation of ROIs have been implicated in certain types of apoptotic cell death. To evaluate the role of TAL in this process, Jurkat human T cells were permanently transfected with TAL expression vectors oriented in the sense or antisense direction. Overexpression of TAL resulted in a decrease in glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and NADPH and GSH levels and rendered these cells highly susceptible to apoptosis induced by serum deprivation, hydrogen peroxide, nitric oxide, tumor necrosis factor-alpha, and anti-Fas monoclonal antibody. In addition, reduced levels of TAL resulted in increased glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and increased GSH levels with inhibition of apoptosis in all five model systems. The effect of TAL expression on susceptibility to apoptosis through regulating the PPP and GSH production is consistent with an involvement of ROIs in each pathway tested. Production of ROIs in Fas-mediated cell death was further substantiated by measurement of intracellular ROI production with oxidation-sensitive fluorescent probes, by the protective effects of GSH precursor, N-acetyl cysteine, free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide, the antioxidants desferrioxamine, nordihydroguaiaretic acid, and Amytal, and by the enhancing effects of GSH depletion with buthionine sulfoximine. The results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals. |
| Databáze: | OpenAIRE |
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