Abstract
Nitric oxide (NO) is known for its diverse activities throughout biology. Among signaling qualities, NO affects cellular decisions of life and death either by turning on apoptotic pathways or by shutting them off. Although copious reports support both notions, the dichotomy of NO actions remains unsolved. Proapoptotic pathways of NO are compatible with established signaling circuits appreciated for mitochondria-dependent roads of death, with some emphasis on the involvement of the tumor suppressor p53 as a target during cell death execution. Antiapoptotic actions of NO are numerous, ranging from an immediate interference with proapoptotic signaling cascades to long-lasting effects based on expression of cell protective proteins with some interest on the ability of NO-redox species to block caspases by S-nitrosylation/S-nitrosation. Summarizing emerging concepts to understand p53 accumulation on the one hand while proposing inhibition of procaspase processing on the other may help to define the pro- versus antiapoptotic roles of NO.
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Abbreviations
- NO:
-
nitric oxide
- NOS:
-
nitric oxide synthase
- iNOS:
-
inducible NOS
- RNI:
-
reactive nitrogen intermediates
- ROI:
-
reactive oxygen intermediates
- Mdm2:
-
murine double minute
- CHOP:
-
C/EBP homologous protein (also known as GADD153)
- MAPK:
-
mitogen activated protein kinases
- DISC:
-
death inducing signaling complex
- CARD:
-
caspase recruitment domain
- Apaf:
-
apoptosis protease activating factor 1
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Acknowledgements
I apologize to researchers whose primary observations that form the basis for our current knowledge in this active field could not be cited because of space limitations. Our work was supported by grants from Deutsche Forschungsgemeinschaft (Br 999), Deutsche Krebshilfe, Sander Foundation and Fonds der Chemischen Industrie.
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Brüne, B. Nitric oxide: NO apoptosis or turning it ON?. Cell Death Differ 10, 864–869 (2003). https://doi.org/10.1038/sj.cdd.4401261
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DOI: https://doi.org/10.1038/sj.cdd.4401261
