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Human T cell leukemia virus-I (HTLV-I) Tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state
Department of Internal Medicine I, Eberhard-Karls University, Tübingen, Germany.ORCID iD: 0000-0001-9518-1411
Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Department of Internal Medicine I, Eberhard-Karls University, Tübingen, Germany; .
Tularik Inc., San Francisco, CA, USA.
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1998 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 161, no 6, 3050-3055 p.Article in journal (Refereed) Published
Abstract [en]

We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis, The present study demonstrates that a hormone-dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2; these changes are followed by apoptotic cell death. Additional stimulation of the CD3/TCR pathway enhances the oxidative and apoptotic effects. Both Tax-mediated apoptosis and oxidative stress can be potently suppressed by antioxidants, as is seen with the administration of recombinant thioredoxin (adult T cell leukemia derived factor) or pyrrolidine dithiocarbamate. Hormone-induced Tax activation induces a long-lasting activation of NF-kappa B, which is a major target of reactive oxygen ntermediates. The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity. A subsequent transfection of these apparently "nonresponsive" clones allows the recovery of Tax responses in these cells. Our observations indicate that changes in the intracellular redox status mag be a determining factor in Tax-mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.

Place, publisher, year, edition, pages
American Association of Immunologists , 1998. Vol. 161, no 6, 3050-3055 p.
Keyword [en]
antioxidants, gene-expression, induction, interleukin-2, lymphocytes, nf-kappa-b, protein, redox regulation, thioredoxin, transcription factor
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-87030ISI: 000075864600050PubMedID: 9743370OAI: oai:DiVA.org:liu-87030DiVA: diva2:584268
Available from: 2013-01-08 Created: 2013-01-08 Last updated: 2017-12-06

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Los, Marek Jan

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