Redox control of hepatic cell death

Hannes Hentze, Markus Latta, Gerald Künstle, Rudolf Lucas, Albrecht Wendel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In necrotic liver failure like upon acetaminophen overdose, loss of the major intracellular thiol antioxidant glutathione was shown to be causal for hepatic dysfunction. In sharp contrast, fulminant apoptotic liver destruction upon overstimulation of the death receptors TNFR1 and CD95 was not associated with reduced hepatic glutathione levels. In view of the importance of the role of reactive oxygen intermediates versus antioxidants for apoptosis, we investigated the effect of phorone-induced enzymatic GSH depletion on the sensitivity of the liver towards CD95- or TNFR1-mediated hepatotoxicity. Our findings demonstrate in vivo that receptor-mediated hepatic apoptosis is disabled when glutathione is depleted, i.e. that an intact glutathione status is a critical determinant for the execution of apoptosis. In vitro, we did mechanistic studies in lymphoid cell lines and found that pro-caspase-8 at the CD95 death receptor and the mitochondrial activation of pro-caspase-9 are the enzyme targets that require sufficient intracellular reduced glutathione for their activation.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalToxicology Letters
Volume139
Issue number2-3
DOIs
StatePublished - Apr 4 2003

Fingerprint

Cell death
Oxidation-Reduction
Glutathione
Hepatocytes
Cell Death
Liver
Receptors, Tumor Necrosis Factor, Type I
Death Domain Receptors
Apoptosis
Antioxidants
Chemical activation
Caspase 9
Caspase 8
Liver Failure
Acetaminophen
Sulfhydryl Compounds
Cells
Lymphocytes
Oxygen
Cell Line

Keywords

  • Apoptosis
  • Death receptors
  • Glutathione
  • Pro-caspase activation

ASJC Scopus subject areas

  • Toxicology

Cite this

Hentze, H., Latta, M., Künstle, G., Lucas, R., & Wendel, A. (2003). Redox control of hepatic cell death. Toxicology Letters, 139(2-3), 111-118. https://doi.org/10.1016/S0378-4274(02)00425-3

Redox control of hepatic cell death. / Hentze, Hannes; Latta, Markus; Künstle, Gerald; Lucas, Rudolf; Wendel, Albrecht.

In: Toxicology Letters, Vol. 139, No. 2-3, 04.04.2003, p. 111-118.

Research output: Contribution to journalArticle

Hentze, H, Latta, M, Künstle, G, Lucas, R & Wendel, A 2003, 'Redox control of hepatic cell death', Toxicology Letters, vol. 139, no. 2-3, pp. 111-118. https://doi.org/10.1016/S0378-4274(02)00425-3
Hentze H, Latta M, Künstle G, Lucas R, Wendel A. Redox control of hepatic cell death. Toxicology Letters. 2003 Apr 4;139(2-3):111-118. https://doi.org/10.1016/S0378-4274(02)00425-3
Hentze, Hannes ; Latta, Markus ; Künstle, Gerald ; Lucas, Rudolf ; Wendel, Albrecht. / Redox control of hepatic cell death. In: Toxicology Letters. 2003 ; Vol. 139, No. 2-3. pp. 111-118.
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