Suppression of Lymphocyte Signal Transduction by Oxygen Intermediates.
Final rept. 30 Sep 95-30 Mar 99
NEW YORK UNIV MEDICAL CENTER TUXEDO NY
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Effect of oxidative stressOS on nuclear signal transduction and on cellular anti-oxidant mechanisms, were compared in human blood lymphocytes. DNA-binding activities of 3 transcription factors TF NFkB, AP-1 and NFAT, were abolished in activated T lymphocytes by all types of OS. Radiation exposure was also studied in B cells and had the same effect as on T cells. Only exposure to the lowest H2O2 concentration induced lipid peroxidation. Enhanced catalase activity was detected upon exposure to oxidative stress. Glutathione peroxidase activity and reduced glutathione, vitamin C and vitamin E levels were not modulated by oxidative stress. N-acetyl cysteine protected human lymphocytes against oxidative stress. Conclusions 1. Suppression of specific TF functions, and IL-2 biosynthesis, can serve as a marker of lymphocyte exposure to OS 2. Based on these results, an in vitro screening assay to identify oxidants, and an assay to monitor human exposures to oxidants, can be developed. 3. Enhanced catalase activity may be developed as a marker for the ability of cells from exposed soldiers to mount an anti-oxidative response. 4. N-acetyl cysteine was identified as a compound that may protect individuals exposed to oxidants.
- Anatomy and Physiology
- Medicine and Medical Research
- Stress Physiology