Glutathione dependence of caspase-8 activation at the death-inducing signaling complex
<p>Apoptosis triggered by the death receptor CD95 (APO-1 or Fas) is pivotal for the homeostasis of the immune system. We investigated differential effects of glutathione depletion on CD95-triggered apoptosis in T and B cell lines as well as the glutathione dependence of caspase-8 activation. I...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 15, 2002
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| In: |
The journal of biological chemistry
Year: 2002, Volume: 277, Issue: 7, Pages: 5588-5595 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M110766200 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M110766200 Verlag, lizenzpflichtig, Volltext: https://www.jbc.org/article/S0021-9258(19)82601-7/abstract 
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| Author Notes: | Hannes Hentze, Ingo Schmitz, Markus Latta, Andreas Krueger, Peter H. Krammer and Albrecht Wendel |
| Summary: | <p>Apoptosis triggered by the death receptor CD95 (APO-1 or Fas) is pivotal for the homeostasis of the immune system. We investigated differential effects of glutathione depletion on CD95-triggered apoptosis in T and B cell lines as well as the glutathione dependence of caspase-8 activation. In B lymphoblastoid SKW6.4 cells, CD95-mediated apoptosis was prevented upstream of caspase-8 activation and caspase-3-like activity after acute glutathione depletion by diethyl maleate or<i>cis</i>-chloro-dinitrobenzene. Immunoprecipitation of the death-inducing signaling complex (DISC) revealed that the DISC was still formed in the glutathione-depleted state. The first cleavage step of procaspase-8 activation at the DISC, however, was inhibited. Accordingly, under cell-free conditions, radiolabeled procaspase-8 was processed at the immunoprecipitated DISC only after the addition of exogenous dithiothreitol or reduced glutathione. We also observed suppression of CD95-mediated apoptosis in glutathione-depleted CEM and H9 cells. Notably, Jurkat cells still died upon CD95 engagement under this condition, displaying incomplete nuclear fragmentation and a partial switch to necrosis; this may be explained by reduced cytochrome<i>c</i>/dATP-mediated caspase activation observed in cytosol from glutathione-depleted Jurkat cytosol. Our data indicate that the activation of caspase-8 at the DISC and hence CD95-mediated apoptosis induction shows a cell-specific requirement for intracellular glutathione.</p> |
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| Item Description: | Gesehen am 15.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M110766200 |