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Updated: Jun 11, 2026
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Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
Published on: July 3, 2025
Cell signaling mediated by nitrated cyclic guanine nucleotide
Takaaki Akaike1, Shigemoto Fujii, Tomohiro Sawa
1Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. takakaik@gpo.kumamoto-u.ac.jp
Nitric Oxide : Biology and Chemistry
|July 6, 2010
Summary
Researchers discovered 8-nitro-cGMP, a novel nitrated cyclic nucleotide and second messenger. This molecule triggers protein S-guanylation, activating protective cellular pathways and offering therapeutic potential.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Signaling
Background:
- Nitric oxide (NO) signaling is crucial in mammals.
- Cyclic guanosine monophosphate (cGMP) has been a known second messenger for over 40 years.
- The discovery of novel signaling molecules in NO pathways is ongoing.
Purpose of the Study:
- To elucidate the physiological formation of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP).
- To identify the roles of 8-nitro-cGMP in nitric oxide (NO) signal transduction.
- To investigate the novel post-translational modification termed protein S-guanylation.
Main Methods:
- Liquid chromatography-tandem mass spectrometry for chemical analysis.
- Cell culture studies using macrophages and glial cells.
- Investigation of protein interactions and post-translational modifications.
Main Results:
- 8-nitro-cGMP formation was identified and confirmed to be dependent on NO production.
- 8-nitro-cGMP acts as an electrophile, inducing protein S-guanylation.
- S-guanylation of the redox-sensor protein Keap1 by 8-nitro-cGMP activates the Nrf2 pathway.
- This activation leads to the induction of cytoprotective genes like heme oxygenase-1.
Conclusions:
- 8-nitro-cGMP is a newly identified nitrated cyclic nucleotide and second messenger in mammals.
- Protein S-guanylation is a novel post-translational modification with significant physiological roles.
- 8-nitro-cGMP and S-guanylation have implications for NO-related physiology, pathology, and therapeutic development.
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