The role of oxygen in thymocyte apoptosis.
Signals generated by T cell receptor (TCR) cross-linking (or phorbol 12-myristate-13-acetate + Ca2+ ionophore), glucocorticoids or ionizing radiation all stimulate apoptotic cell death in thymocytes by signals that are initially distinct from each other. However, when these stimuli were administered to thymocyte cultures that were maintained under an atmosphere containing less than 20 ppm oxygen as opposed to one that contained 18.5% molecular oxygen, cell death was inhibited or abrogated, suggesting that the induction of death by all three different stimuli depend on the presence of molecular oxygen. Studies of the effects of the cysteine analog N-acetyl cysteine (NAC) with normal thymocytes demonstrated that this antioxidant inhibited the induction of death by each of the different stimuli in a manner the paralleled anaerobiosis. Furthermore, studies with thymocytes demonstrated that the induction of nur77, a gene shown to be involved in thymocyte apoptosis signaled through the TCR or its surrogates, is not inhibited by NAC or dependent upon molecular oxygen. The possible implications for negative selection of NAC-mediated inhibition of TCR-signaled thymocyte cell death was examined in thymic organ culture. Treatment of these cultures with NAC provided significant protection against staphylococcal enterotoxin B-mediated deletion of V beta 8-expressing thymocytes.
McLaughlin
K A
KA
Program in Molecular and Cellular Biology, University of Massachusetts, Amherst 01002, USA.
Osborne
B A
BA
Goldsby
R A
RA
D000111:Acetylcysteine / Q000494:pharmacology; D000693:Anaerobiosis / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D000001:Calcimycin / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D004768:Enterotoxins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000001:Calcimycin; C031818:enterotoxin B, staphylococcal; D008623:Mercaptoethanol; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D000111:Acetylcysteine