Role of Reactive Oxygen Intermediates in Activation-induced CD95 (APO-1/Fas) Ligand Expression
T-Lymphocytes
610
Apoptosis
Lymphocyte Activation
fas-mediated apoptosis
involvement
Biochemistry
Antioxidants
Jurkat Cells
03 medical and health sciences
nf-kappa-b
oxidative stress
Humans
fas Receptor
Biokemi
Molecular Biology
t-cells
hiv-1 tat
programmed cell-death
0303 health sciences
Molekylärbiologi
NF-kappa B
immune-system
cytotoxicity
tumor-necrosis-factor
Reactive Oxygen Species
DOI:
10.1074/jbc.273.14.8048
Publication Date:
2002-07-26T15:13:03Z
AUTHORS (6)
ABSTRACT
Activation-induced cell death of T lymphocytes requires the inducible expression of CD95 (APO-1/Fas) ligand, which triggers apoptosis in CD95-bearing target cells by an autocrine or paracrine mechanism. Although execution of the CD95 death pathway is largely independent of reactive oxygen intermediates, activation-induced cell death is blocked by a variety of antioxidants. In the present study, we investigated the involvement of redox processes in the regulation of CD95 ligand (CD95L) expression in Jurkat T cells. We show that various antioxidants potently inhibited the transcriptional activation of CD95L following T cell receptor ligation or stimulation of cells with phorbol ester and ionomycin. Conversely, a prooxidant such as hydrogen peroxide alone was able to increase CD95L expression. As detected by Western blot and cytotoxicity assays, functional expression of CD95L protein was likewise diminished by antioxidants. Inhibition of CD95L expression was associated with a decreased DNA binding activity of nuclear factor (NF)-kappaB, an important redox-controlled transcription factor. Moreover, inhibition of NF-kappaB activity by a transdominant IkappaB mutant attenuated CD95L expression. Our data suggest that, although reactive oxygen intermediates do not act as mediators in the execution phase of CD95-mediated apoptosis, they are involved in the transcriptional regulation of CD95L expression.
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