Nitrosopersulfide (SSNO⁻) Is a Unique Cysteine Polysulfidating Agent with Reduction-Resistant Bioactivity

Abstract

Aims:The aim of the present study was to investigate the biochemical properties of nitrosopersulfide (SSNO -), a key intermediate of the nitric oxide (NO)/sulfide cross talk. Results: We obtained corroborating evidence that SSNOis indeed a major product of the reaction of S-nitrosothiols with hydrogen sulfide (H 2 S). It was found to be relatively stable (t 1/2 *1 h at room temperature) in aqueous solution of physiological pH, stabilized by the presence of excess sulfide and resistant toward reduction by other thiols. Furthermore, we here show that SSNOescapes the reducing power of the NADPHdriven biological reducing machineries, the thioredoxin and glutathione reductase systems. The slow decomposition of SSNOproduces inorganic polysulfide species, which effectively induce per/polysulfidation on glutathione or protein cysteine (Cys) residues. Our data also demonstrate that, in contrast to the transient activation by inorganic polysulfides, SSNOinduces long-term potentiation of TRPA1 (transient receptor potential ankyrin 1) channels, which may be due to its propensity to generate a slow flux of polysulfide in situ. Innovation: The characterized properties of SSNOwould seem to represent unique features in cell signaling by enabling sulfur and nitrogen trafficking within the reducing environment of the cytosol, with targeted release of both NO and polysulfide equivalents. Conclusion: SSNOis a surprisingly stable bioactive product of the chemical interaction of S-nitrosothiol species and H 2 S that is resistant to reduction by the thioredoxin and glutathione systems. As well as generating NO, it releases inorganic polysulfides, enabling transfer of sulfane sulfur species to peptide/protein Cys residues. The sustained activation of TRPA1 channels by SSNOis most likely linked to all these properties.

Cardiovascular “Patterns” of H2S and SSNO−-Mix Evaluated from 35 Rat Hemodynamic Parameters

“…administration. Since SSNO − was proposed to be the major longer-lived product of the sulfide and S-nitrosothiols reaction [ 14 , 18 , 19 ], we hereinafter refer to the products of the reaction mixture as the “SSNO − -mix”. The concentration of the SSNO − -mix is defined as the initial concentration of GSNO in the mixture when the reaction time equals zero.…”

Hydrogen Sulfide (H2S) and Polysulfide (H2Sn) Signaling: The First 25 Years

“…Based on these observations, H 2 S n are potential chemical entities produced from H 2 S and NO [ 23 , 37 , 38 ]. Bogdandi et al recently suggested that H 2 S n transiently activate TRPA1 channels at the early phase of the production from H 2 S and NO, while the more stable product SSNO − sustainably activates the channels [ 39 ].…”

The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

“…These species could result in multiple effects including cysteine per- and poly-sulfidation ( vide supra ); however, the likelihood of their formation under biological conditions (with low concentrations of sulfide and •NO or alternative more abundant reactants) is not clear ( Kevil et al., 2017 ). ONSS − in particular has a relatively long lifetime and exhibits potent in vivo hypotensive activity, suggesting potential biological relevance ( Cortese-Krott et al., 2015 ; Bogdandi et al., 2020 ).…”