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[Pro- and anti-apoptotic role of nitric oxide, NO]
1U365 Inserm, Institut Curie, 26, rue d'Ulm, 75248, Paris, France. jpkolb@curie.fr
Abstract:
NO displays both pro- and anti-apoptotic properties. The parameters governing these effects begin to be elucidated. Among these figure the nature of the cells, their redox state, the flow and concentration of NO, its possibility to react with superoxide generated at the level of mitochondria. The targets of NO include molecules involved in DNA repair, such as PARP, the DNA-dependent protein kinase (DNA-PK) and p53 which control the transcription of various genes involved in the apoptotic process (bax, cdk inhibitors), and the proteasome which control the degradation of several apoptotic proteins. The inhibition by NO of caspases through S-nitrosylation of their active sites provides a rationale for our understanding of the anti-apoptotic effect of NO, but other mechanisms are involved, such as a regulation of the mitochondrial permeability. A better knowledge of the various steps of the apoptotic process that are affected by NO would allow the design of new pharmacological tools.
Insights
Nitric oxide (NO) has dual roles in apoptosis, acting as both a pro- and anti-apoptotic agent. Understanding NO
Area of Science:
- Biochemistry and Molecular Biology
- Cell Biology
- Physiology
Context:
- Nitric oxide (NO) exhibits complex, context-dependent roles in cellular processes.
- Apoptosis, or programmed cell death, is a critical cellular mechanism.
- The dual pro- and anti-apoptotic effects of NO are not fully understood.
Purpose:
- To elucidate the parameters that govern the pro- and anti-apoptotic effects of NO.
- To identify the cellular targets and molecular mechanisms through which NO influences apoptosis.
- To explore the potential for developing pharmacological tools based on NO's apoptotic effects.
Summary:
- NO's effects on apoptosis are influenced by cell type, redox state, and NO concentration.
- Key targets of NO include DNA repair enzymes (PARP, DNA-PK), p53, and the proteasome.
- NO inhibits caspases via S-nitrosylation and regulates mitochondrial permeability, contributing to its anti-apoptotic actions.
Impact:
- Provides a deeper understanding of NO's intricate role in apoptosis regulation.
- Highlights molecular targets for potential therapeutic interventions in diseases involving apoptosis.
- Lays the groundwork for designing novel pharmacological agents targeting NO-mediated apoptotic pathways.