Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide

Tomohiro Sawa, Hideshi Ihara, Tomoaki Ida, Shigemoto Fujii, Motohiro Nishida, Takaaki Akaike

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a unique derivative of guanosine 3',5'- cyclic monophosphate (cGMP) formed in mammalian and plant cells in response to production of nitric oxide and reactive oxygen species. 8-Nitro-cGMP possesses signaling activity inherited from parental cGMP, including induction of vasorelaxation through activation of cGMP-dependent protein kinase. On the other hand, 8-nitro-cGMP mediates cellular signaling that is not observed for native cGMP, e.g., it behaves as an electrophile and reacts with protein sulfhydryls, which results in cGMP adduction to protein sulfhydryls (protein S-guanylation). Several proteins have been identified as targets for endogenous protein S-guanylation, including Kelch-like ECH-associated protein 1 (Keap1), H-Ras, and mitochondrial heat shock proteins. 8-Nitro-cGMP signaling via protein S-guanylation of those proteins may have evolved to convey adaptive cellular stress responses. 8-Nitro-cGMP may not undergo conventional cGMP metabolism because of its resistance to phosphodiesterases. Hydrogen sulfide has recently been identified as a potent regulator for metabolisms of electrophiles including 8-nitro-cGMP, through sulfhydration of electrophiles, e.g., leading to the formation of 8-SH-cGMP. Better understanding of the molecular basis for the formation, signaling functions, and metabolisms of 8-nitro-cGMP would be useful for the development of new diagnostic approaches and treatment of diseases related to oxidative stress and redox metabolisms.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume34
DOIs
Publication statusPublished - Jan 1 2013

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Cyclic Nucleotides
Metabolism
Protein S
Proteins
Cell signaling
Cyclic GMP-Dependent Protein Kinases
Hydrogen Sulfide
Oxidative stress
8-nitroguanosine 3',5'-cyclic monophosphate
Mitochondrial Proteins
Cyclic GMP
Phosphoric Diester Hydrolases
Plant Cells
Heat-Shock Proteins
Vasodilation
Oxidation-Reduction
Reactive Oxygen Species
Nitric Oxide
Oxidative Stress
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide. / Sawa, Tomohiro; Ihara, Hideshi; Ida, Tomoaki; Fujii, Shigemoto; Nishida, Motohiro; Akaike, Takaaki.

In: Nitric Oxide - Biology and Chemistry, Vol. 34, 01.01.2013, p. 10-18.

Research output: Contribution to journalReview article

Sawa, Tomohiro ; Ihara, Hideshi ; Ida, Tomoaki ; Fujii, Shigemoto ; Nishida, Motohiro ; Akaike, Takaaki. / Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide. In: Nitric Oxide - Biology and Chemistry. 2013 ; Vol. 34. pp. 10-18.
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