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Nitrosopersulfide (SSNO-) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide

Nitrosopersulfide (SSNO-) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide
Nitrosopersulfide (SSNO-) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide
Sulfide salts are known to promote the release of nitric oxide (NO) from S-nitrosothiols and potentiate their vasorelaxant activity, but much of the cross-talk between hydrogen sulfide and NO is believed to occur via functional interactions of cell regulatory elements such as phosphodiesterases. Using RFL-6 cells as an NO reporter system we sought to investigate whether sulfide can also modulate nitrosothiol-mediated soluble guanylyl cyclase (sGC)activation following direct chemical interaction. We find a U-shaped dose response relationship where low sulfide concentrations attenuate sGC stimulation by Snitrosopenicillamine(SNAP) and cyclic GMP levels are restored at equimolar ratios. Similar results are observed when intracellular sulfide levels are raised by pre-incubation with the sulfide donor, GYY4137. The outcome of direct sulfide/nitrosothiol interactions also critically depends on molar reactant ratios and is accompanied by oxygen consumption. With sulfide in excess, a ‘yellow compound’ accumulates that is indistinguishable from the product 2 of solid-phase transnitrosation of either hydrosulfide or hydrodisulfide and assigned to be nitrosopersulfide (perthionitrite, SSNO-; ?max 412 nm in aqueous buffers, pH 7.4; 448 nm in DMF). Time-resolved chemiluminescence and UV-visible spectroscopy analyses suggest that its generation is preceded by formation of the short-lived NO-donor, thionitrite (SNO-). In contrast to the latter, SSNO- is rather stable at physiological pH and generates both NO and polysulfides on decomposition, resulting in sustained potentiation of SNAP-induced sGC stimulation. Thus, sulfide reacts with nitrosothiols to form multiple bioactive products;SSNO- rather than SNO- may account for some of the longer-lived effects of nitrosothiols and contribute to sulfide and NO signaling.
hydrogen sulfide, nitric oxide, polysulfides, cGMP, HSNO, nitroxyl
2213-2317
234-244
Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Santos, José L.T.
8aa07a54-416d-4835-a632-bf4292daf7d1
Mergia, Evanthia
5995104b-0e4d-4cf6-9eee-350403c139bb
Grman, Marian
0311d132-fea8-4c83-8220-e48eab83fd17
Nagy, Péter
ef870ecd-2ce8-494f-86da-7260d2a7c2a4
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Butler, Anthony
6fe6f7f2-2739-4edb-8868-1962c0d68c03
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cortese-Krott, Miriam M.
7dc9b44c-847c-4196-8866-a3cc0c1dc357
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Santos, José L.T.
8aa07a54-416d-4835-a632-bf4292daf7d1
Mergia, Evanthia
5995104b-0e4d-4cf6-9eee-350403c139bb
Grman, Marian
0311d132-fea8-4c83-8220-e48eab83fd17
Nagy, Péter
ef870ecd-2ce8-494f-86da-7260d2a7c2a4
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Butler, Anthony
6fe6f7f2-2739-4edb-8868-1962c0d68c03
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Cortese-Krott, Miriam M., Fernandez, Bernadette O., Santos, José L.T., Mergia, Evanthia, Grman, Marian, Nagy, Péter, Kelm, Malte, Butler, Anthony and Feelisch, Martin (2014) Nitrosopersulfide (SSNO-) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide. Redox Biology, 2, 234-244. (doi:10.1016/j.redox.2013.12.031). (PMID:24494198)

Record type: Article

Abstract

Sulfide salts are known to promote the release of nitric oxide (NO) from S-nitrosothiols and potentiate their vasorelaxant activity, but much of the cross-talk between hydrogen sulfide and NO is believed to occur via functional interactions of cell regulatory elements such as phosphodiesterases. Using RFL-6 cells as an NO reporter system we sought to investigate whether sulfide can also modulate nitrosothiol-mediated soluble guanylyl cyclase (sGC)activation following direct chemical interaction. We find a U-shaped dose response relationship where low sulfide concentrations attenuate sGC stimulation by Snitrosopenicillamine(SNAP) and cyclic GMP levels are restored at equimolar ratios. Similar results are observed when intracellular sulfide levels are raised by pre-incubation with the sulfide donor, GYY4137. The outcome of direct sulfide/nitrosothiol interactions also critically depends on molar reactant ratios and is accompanied by oxygen consumption. With sulfide in excess, a ‘yellow compound’ accumulates that is indistinguishable from the product 2 of solid-phase transnitrosation of either hydrosulfide or hydrodisulfide and assigned to be nitrosopersulfide (perthionitrite, SSNO-; ?max 412 nm in aqueous buffers, pH 7.4; 448 nm in DMF). Time-resolved chemiluminescence and UV-visible spectroscopy analyses suggest that its generation is preceded by formation of the short-lived NO-donor, thionitrite (SNO-). In contrast to the latter, SSNO- is rather stable at physiological pH and generates both NO and polysulfides on decomposition, resulting in sustained potentiation of SNAP-induced sGC stimulation. Thus, sulfide reacts with nitrosothiols to form multiple bioactive products;SSNO- rather than SNO- may account for some of the longer-lived effects of nitrosothiols and contribute to sulfide and NO signaling.

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e-pub ahead of print date: 10 January 2014
Keywords: hydrogen sulfide, nitric oxide, polysulfides, cGMP, HSNO, nitroxyl
Organisations: Faculty of Medicine

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Local EPrints ID: 361504
URI: http://eprints.soton.ac.uk/id/eprint/361504
ISSN: 2213-2317
PURE UUID: 09e73432-eb36-41ce-ab51-2cb579193560
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 23 Jan 2014 16:01
Last modified: 15 Mar 2024 03:45

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Contributors

Author: Miriam M. Cortese-Krott
Author: Bernadette O. Fernandez ORCID iD
Author: José L.T. Santos
Author: Evanthia Mergia
Author: Marian Grman
Author: Péter Nagy
Author: Malte Kelm
Author: Anthony Butler
Author: Martin Feelisch ORCID iD

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