Optimal NFκB Mediated Transcriptional Responses in Jurkat T Cells Exposed to Oxidative Stress Are Dependent on Intracellular Glutathione and Costimulatory Signals
| Autor: | Margaret E. Ginn-Pease, Ronald L. Whisler |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
Transcriptional Activation P50 Transcription Genetic CD3 Biophysics medicine.disease_cause Biochemistry Jurkat cells Jurkat Cells chemistry.chemical_compound Transactivation Genes Reporter medicine Humans Phytohemagglutinins Buthionine Sulfoximine Molecular Biology Cell Nucleus Binding Sites biology NF-kappa B Hydrogen Peroxide Cell Biology Glutathione NFKB1 Molecular biology Kinetics Oxidative Stress Oligodeoxyribonucleotides chemistry biology.protein Phorbol Tetradecanoylphorbol Acetate Oxidative stress Muromonab-CD3 Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 226:695-702 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1996.1416 |
| Popis: | Many early response genes induced by the exposure of mammalian cells to environmental stress contain DNA sequences which bind nuclear factor (NF) kappa B. However, the effects of oxidative stress on NF kappa B activity in T cells are contradictory with evidence supporting both stimulation and suppression. The present investigation examined the effects of low levels of oxidative stress in the form of H2O2 on NF kappa B transactivation in Jurkat T cells and the regulation of NF kappa B activity by cellular glutathione (GSH) levels and costimulatory signals. Transient transfection analyses demonstrated 2-3 fold increases in transcription of an NF kappa B dependent chloramphenicol acetyl transferase (CAT) reporter after the exposure of Jurkat cells to 100-500 microM H2O2. By comparison, dual stimulation of Jurkat cells with phytohemagglutinin (PHA) plus phorbol (PMA) induced 9-10 fold increases in NF kappa B CAT activity. Although no marked changes in GSH levels were detected in cells treated with H2O2 or PHA/PMA, the depletion of GSH in cells pretreated with DL-buthionine-[S,R]-sulfoximine (BSO) substantially inhibited NF kappa B transactivation by H2O2. In addition, H2O2 was less effective than PHA/PMA in inducing NF kappa B1 (p50)/RelA (p65) complexes. However, signals induced by oxidative conditions effectively cooperated with stimulatory signals provided by PMA but not with T cell receptor/CD3 stimulation to induce significant increases in NF kappa B CAT responses. These results suggest that a functional GSH system is required for NF kappa B activation in T cells exposed to oxidative reagents and provide evidence that oxidative stress triggers signaling events capable of participating with distinct coregulatory signals to activate NF kappa B transcriptional responses. |
| Databáze: | OpenAIRE |
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