Glutathione dependence of caspase-8 activation at the death-inducing signaling complex

• Verfasst von: Hentze, Hannes [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Glutathione dependence of caspase-8 activation at the death-inducing signaling complex
• Verf.angabe: Hannes Hentze, Ingo Schmitz, Markus Latta, Andreas Krueger, Peter H. Krammer and Albrecht Wendel
• E-Jahr: 2002
• Jahr: February 15, 2002
• Umfang: 8 S.
• Teil: volume:277
• Teil: year:2002
• Teil: number:7
• Teil: pages:5588-5595
• Teil: extent:8
• Fussnoten: Gesehen am 15.04.2021
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : Soc., 1905
• Jahr Quelle: 2002
• Band/Heft Quelle: 277(2002), 7, Seite 5588-5595
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M110766200
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1755022042

Abstract

<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>