Nitrosopersulfide (SSNO - ) is a unique cysteine polysulfidating agent with reduction-resistant bioactivity.
2020
AIMS: The aim of the present study was to investigate the biochemical properties of nitrosopersulfide (SSNO-), a key intermediate of the NO/sulfide crosstalk. RESULTS: We obtained corroborating evidence that SSNO- is indeed a major product of the reaction of S-nitrosothiols with H2S. It was found to be relatively stable (t1/2 ~1h at RT) in aqueous solution of physiological pH, stabilized by the presence of excess sulfide and resistant towards reduction by other thiols. Furthermore, we here show that SSNO- escapes the reducing power of the NADPH-driven biological reducing machineries, the thioredoxin and glutathione reductase systems. The slow decomposition of SSNO- produces inorganic polysulfide species, which effectively induce per/polysulfidation on glutathione or protein Cys residues. Our data also demonstrate that, in contrast to the transient activation by inorganic polysulfides, SSNO- induces long-term potentiation of TRPA1 channels, which may be due to its propensity to generate a slow flux of polysulfide in situ. INNOVATION: The characterized properties of SSNO- would 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: SSNO- is a surprisingly stable bioactive product of the chemical interaction of S-nitrosothiol species and H2S 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/proteine Cys residues. The sustained activation of TRPA1 channels by SSNO- is most likely linked to all these properties.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
6
Citations
NaN
KQI