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Nitric oxide can inhibit apoptosis or switch it into necrosis
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
Summary
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.