Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation

Gerry Melino, Francesca Bernassola, Maria Valeria Catani, Antonello Rossi, Marco Corazzari, Stefania Sabatini, Francis Vilbois, Douglas R. Green

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Several inducers of cytotoxic stress promote apoptotic cell death, which, at least in some cases, involves the CD95/CD95 ligand (CD95L) pathway. The induction of the CD95/CD95L pathway can be activated by the activator protein-1 (AP-1)-mediated up-regulation of the CD95L promoter, which is responsible for the induction of apoptosis elicited by stimuli such as etoposide. We show that nitric oxide (NO) represents a regulatory element able to block apoptosis by interfering with this loop. Etoposide- and C6- ceramide-induced apoptosis in Jurkat T cells with different kinetics. Cell death was accompanied by an increase in DNA-binding activity of the transcription factor AP-1, transactivation of the AP-1 site-containing CD95L promoter, and caspase 3-like protease activation. Using different NO- releasing compounds, we found that apoptosis was prevented in a dose- dependent manner. Furthermore, in both models of apoptosis, NO-releasing compounds dose-dependently reduced: (a) the number of the titratable thiol groups (cysteine residues) of c-Jun; (b) induction of AP-1 DNA-binding activity; (c) AP-1-driven transactivation of the CD95L promoter; and (d) caspase activation. In conclusion, our data demonstrate that NO can modulate cell death at an upstream level, by interfering with the ability of AP-1 to induce CD95L expression.

Original languageEnglish
Pages (from-to)2377-2383
Number of pages7
JournalCancer Research
Volume60
Issue number9
Publication statusPublished - May 1 2000

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Fas Ligand Protein
Transcription Factor AP-1
Transcriptional Activation
Nitric Oxide
Apoptosis
Cell Death
Etoposide
Jurkat Cells
DNA
Caspases
Sulfhydryl Compounds
Caspase 3
Cysteine
Peptide Hydrolases
Transcription Factors
Up-Regulation
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Melino, G., Bernassola, F., Catani, M. V., Rossi, A., Corazzari, M., Sabatini, S., ... Green, D. R. (2000). Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation. Cancer Research, 60(9), 2377-2383.

Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation. / Melino, Gerry; Bernassola, Francesca; Catani, Maria Valeria; Rossi, Antonello; Corazzari, Marco; Sabatini, Stefania; Vilbois, Francis; Green, Douglas R.

In: Cancer Research, Vol. 60, No. 9, 01.05.2000, p. 2377-2383.

Research output: Contribution to journalArticle

Melino, G, Bernassola, F, Catani, MV, Rossi, A, Corazzari, M, Sabatini, S, Vilbois, F & Green, DR 2000, 'Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation', Cancer Research, vol. 60, no. 9, pp. 2377-2383.
Melino G, Bernassola F, Catani MV, Rossi A, Corazzari M, Sabatini S et al. Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation. Cancer Research. 2000 May 1;60(9):2377-2383.
Melino, Gerry ; Bernassola, Francesca ; Catani, Maria Valeria ; Rossi, Antonello ; Corazzari, Marco ; Sabatini, Stefania ; Vilbois, Francis ; Green, Douglas R. / Nitric oxide inhibits apoptosis via AP-1-dependent CD95L transactivation. In: Cancer Research. 2000 ; Vol. 60, No. 9. pp. 2377-2383.
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