Oxidative stress suppresses transcription factor activities in stimulated lymphocytes.
Effects of oxidative stress on stimulation-dependent signal transduction, leading to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells were then stimulated for 6 h. DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NFkappaB, AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 microM). All three modes of oxidative stress induced catalase activity in the lymphocytes. The only exception was hydrogen peroxide at 20 microM, which did not induce catalase activity. We conclude that: (i) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes; (ii) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (iii) therefore, transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation.
Flescher
E
E
Department of Environmental Medicine, New York University Medical Center, Tuxedo 10987, USA.
Tripoli
H
H
Salnikow
K
K
Burns
F J
FJ
D002374:Catalase; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects; D008995:Monoamine Oxidase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008054:Lipid Peroxides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D017665:Hydroxyl Radical; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D008995:Monoamine Oxidase