8-Nitro-cGMP: A novel protein-reactive cNMP and its emerging roles in autophagy

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

Nitric oxide (NO) raises the intracellular 3′,5′-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO2) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs. Multiple studies suggest that its intracellular abundance might exceed that of unmodified cGMP. The characteristic chemical feature of 8-nitro-cGMP is its ability to modify proteinous cysteine residues via a stable sulfide bond. In this posttranslational modification, the nitro group is detached from the guanine base. This modification, termed “protein S-guanylation,” is known to regulate the physiological functions of several important proteins. Furthermore, 8-nitro-cGMP participates in the regulation of autophagy. For example, in antibacterial autophagy (xenophagy), S-guanylation accumulates around invading bacterial cells and functions as a “tag” for subsequent clearance of the organism via ubiquitin modifications. This finding suggests the existence of a system for recognizing the cGMP structure on proteins. Autophagy induction by 8-nitro-cGMP is mechanistically distinct from the well-described starvation-induced autophagy and is independent of the action of mTOR, the master regulator of canonical autophagy.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages253-268
Number of pages16
DOIs
Publication statusPublished - 2017 Jan 1

Publication series

NameHandbook of Experimental Pharmacology
Volume238
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • 8-Amino-cGMP
  • 8-Nitro-cGMP
  • 8-SH-cGMP
  • Autophagy
  • S-Guanylation
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Arimoto, H., & Takahashi, D. (2017). 8-Nitro-cGMP: A novel protein-reactive cNMP and its emerging roles in autophagy. In Handbook of Experimental Pharmacology (pp. 253-268). (Handbook of Experimental Pharmacology; Vol. 238). Springer New York LLC. https://doi.org/10.1007/164_2016_5000