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Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression
Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Tübingen.
Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Tübingen.
Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Tübingen, Germany.ORCID-id: 0000-0001-9518-1411
Department of Virology, Albrecht-Ludwigs-University, Freiburg, Germany.
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1998 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 273, nr 14, s. 8048-8055Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 litigation 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)-kappa B, an important redox-controlled transcription factor. Moreover, inhibition of NF-kappa B activity by a transdominant I kappa B 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.

Ort, förlag, år, upplaga, sidor
1998. Vol. 273, nr 14, s. 8048-8055
Nyckelord [en]
cytotoxicity, fas-mediated apoptosis, hiv-1 tat, immune-system, involvement, nf-kappa-b, oxidative stress, programmed cell-death, t-cells, tumor-necrosis-factor
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Biokemi och molekylärbiologi
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URN: urn:nbn:se:liu:diva-87065DOI: 10.1074/jbc.273.14.8048ISI: 000072876300039PubMedID: 9525905OAI: oai:DiVA.org:liu-87065DiVA, id: diva2:584760
Tillgänglig från: 2013-01-09 Skapad: 2013-01-09 Senast uppdaterad: 2017-12-06

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