Nitric oxide can inhibit apoptosis or switch it into necrosis

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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

G Melino1, M V Catani, M Corazzari

  • 1IDI-IRCCS, Department of Experimental Medicine, University of Rome Tor Vergata, Italy. gerry.melino@uniroma2.it

Cellular and Molecular Life Sciences : CMLS
|December 29, 2000
PubMed

Insights

Nitric oxide (NO) regulates cell death by S-nitrosylation, modulating protein function to either prevent apoptosis or promote necrosis. This signaling molecule impacts neuroblastoma and T-cell survival pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Nitric oxide (NO) acts as a crucial signaling molecule in various physiological and pathological processes.
  • S-nitrosylation, a redox modification of protein thiols, influences protein function and cellular signaling.
  • NO's role in apoptosis is complex, capable of both inhibiting cell death and inducing necrosis.

Purpose of the Study:

  • To investigate the dual role of nitric oxide (NO) in regulating apoptosis and necrosis in different cell types.
  • To explore the mechanism of NO-mediated cell death regulation through S-nitrosylation of key proteins.

Main Methods:

  • Utilized neuroblastoma and Jurkat T cell models to study apoptosis and necrosis.
  • Investigated the effects of NO on retinoid-, cisplatin-, anti-CD95-, and ceramide-induced cell death.
  • Examined the S-nitrosylation of critical apoptotic factors like caspases and tissue transglutaminase.

Main Results:

  • NO protected neuroblastoma cells from apoptosis induced by retinoids and cisplatin, without increasing necrosis.
  • S-nitrosylation of active-site cysteines in caspases and tissue transglutaminase inhibited their catalytic activity, suggesting a role in cell survival.
  • In Jurkat T cells, NO shifted anti-CD95- and ceramide-triggered apoptosis towards necrotic cell death, indicating context-dependent effects.

Conclusions:

  • Nitric oxide exhibits context-dependent regulation of cell death, acting as a survival factor in some instances and promoting necrosis in others.
  • S-nitrosylation of key apoptotic proteins by NO is a significant mechanism for modulating cell fate.
  • NO's influence on cell death pathways may depend on the specific apoptotic stimulus and cellular context, potentially acting downstream of critical signaling events.

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