TY - JOUR
T1 - Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state
AU - Los, Marek
AU - Khazaie, Khashayarsha
AU - Schulze-Osthoff, Klaus
AU - Baeuerle, Patrick A.
AU - Schirrmacher, Volker
AU - Chlichlia, Katerina
PY - 1998/9/15
Y1 - 1998/9/15
N2 - 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-κB, which is a major target of reactive oxygen intermediates. 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 may be a determining factor in Tax- mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.
AB - 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-κB, which is a major target of reactive oxygen intermediates. 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 may be a determining factor in Tax- mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.
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M3 - Article
C2 - 9743370
AN - SCOPUS:0032531092
SN - 0022-1767
VL - 161
SP - 3050
EP - 3055
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -