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Nitrosopersulfide (SSNO-) is a unique cysteine polysulfidating agent with reduction-resistant bioactivity

Nitrosopersulfide (SSNO-) is a unique cysteine polysulfidating agent with reduction-resistant bioactivity
Nitrosopersulfide (SSNO-) is a unique cysteine polysulfidating agent with reduction-resistant bioactivity

AIMS: The aim of the present study was to investigate the biochemical properties of nitrosopersulfide (SSNO<sup>-</sup>), a key intermediate of the NO/sulfide crosstalk.

RESULTS: We obtained corroborating evidence that SSNO<sup>-</sup> is indeed a major product of the reaction of S-nitrosothiols with H<sub>2</sub>S. It was found to be relatively stable (t<sub>1/2</sub> ~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<sup>-</sup> escapes the reducing power of the NADPH-driven biological reducing machineries, the thioredoxin and glutathione reductase systems. The slow decomposition of SSNO<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> is most likely linked to all these properties.

TRPA1, hydrogen sulfide, nitric oxide, persulfidation, redox signaling
1523-0864
1277-1294
Bogdándi, Virág
8938002e-9f5b-46d8-8ccf-6660b0fe507f
Ditrói, Tamás
1b8e16f5-c15f-44f2-98d0-ca2b431a2342
Bátai, Zoárd István
dbafc2ab-4dd7-48f9-83c7-d97c70d6e9b7
Sándor, Zoltán
e2836dae-0f51-4abb-bb88-863602de2c22
Minnion, Magda
ab23b32b-9f8e-4876-aaf5-99cb6a725a2f
Vasas, Anita
6861b2ff-e0b7-40f1-9db7-5a8627fe0d16
Galambos, Klaudia
1772d919-731a-4a8b-a510-439b148d4ce5
Buglyó, Péter
ba90ce4b-90e0-49a6-bf94-ee24fe3d0173
Pintér, Erika
82f3fdaa-29fb-43e8-8277-f036662c5a0d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Nagy, Peter
1c1ec453-5922-4e81-ad91-759d512472b7
Bogdándi, Virág
8938002e-9f5b-46d8-8ccf-6660b0fe507f
Ditrói, Tamás
1b8e16f5-c15f-44f2-98d0-ca2b431a2342
Bátai, Zoárd István
dbafc2ab-4dd7-48f9-83c7-d97c70d6e9b7
Sándor, Zoltán
e2836dae-0f51-4abb-bb88-863602de2c22
Minnion, Magda
ab23b32b-9f8e-4876-aaf5-99cb6a725a2f
Vasas, Anita
6861b2ff-e0b7-40f1-9db7-5a8627fe0d16
Galambos, Klaudia
1772d919-731a-4a8b-a510-439b148d4ce5
Buglyó, Péter
ba90ce4b-90e0-49a6-bf94-ee24fe3d0173
Pintér, Erika
82f3fdaa-29fb-43e8-8277-f036662c5a0d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Nagy, Peter
1c1ec453-5922-4e81-ad91-759d512472b7

Bogdándi, Virág, Ditrói, Tamás, Bátai, Zoárd István, Sándor, Zoltán, Minnion, Magda, Vasas, Anita, Galambos, Klaudia, Buglyó, Péter, Pintér, Erika, Feelisch, Martin and Nagy, Peter (2020) Nitrosopersulfide (SSNO-) is a unique cysteine polysulfidating agent with reduction-resistant bioactivity. Antioxidants & Redox Signaling, 33 (18), 1277-1294. (doi:10.1089/ars.2020.8049).

Record type: Article

Abstract

AIMS: The aim of the present study was to investigate the biochemical properties of nitrosopersulfide (SSNO<sup>-</sup>), a key intermediate of the NO/sulfide crosstalk.

RESULTS: We obtained corroborating evidence that SSNO<sup>-</sup> is indeed a major product of the reaction of S-nitrosothiols with H<sub>2</sub>S. It was found to be relatively stable (t<sub>1/2</sub> ~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<sup>-</sup> escapes the reducing power of the NADPH-driven biological reducing machineries, the thioredoxin and glutathione reductase systems. The slow decomposition of SSNO<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> 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<sup>-</sup> is most likely linked to all these properties.

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2020 Bogdani ARS-accepted ms - Accepted Manuscript
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e-pub ahead of print date: 22 April 2020
Keywords: TRPA1, hydrogen sulfide, nitric oxide, persulfidation, redox signaling

Identifiers

Local EPrints ID: 439795
URI: http://eprints.soton.ac.uk/id/eprint/439795
ISSN: 1523-0864
PURE UUID: e177c8ba-46f6-468a-9842-d594e1372229
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 04 May 2020 16:34
Last modified: 28 Apr 2022 04:15

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Contributors

Author: Virág Bogdándi
Author: Tamás Ditrói
Author: Zoárd István Bátai
Author: Zoltán Sándor
Author: Magda Minnion
Author: Anita Vasas
Author: Klaudia Galambos
Author: Péter Buglyó
Author: Erika Pintér
Author: Martin Feelisch ORCID iD
Author: Peter Nagy

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