Nitrosopersulfide (SSNO) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide
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 S-nitrosopenicillamine (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 of solid-phase transnitrosation of either hydrosulfide or hydrodisulfide and assigned to be nitrosopersulfide (perthionitrite, SSNO; λ 412nm in aqueous buffers, pH 7.4; 448nm 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.
Citation
Cortese-Krott , M M , Fernandez , B O , Santos , J L T , Mergia , E , Grman , M , Nagy , P , Kelm , M , Butler , A & Feelisch , M 2014 , ' Nitrosopersulfide (SSNO) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide ' , Redox Biology , vol. 2 , no. 1 , pp. 234-244 . https://doi.org/10.1016/j.redox.2013.12.031
Publication
Redox Biology
Status
Peer reviewed
ISSN
2213-2317Type
Journal article
Description
Funding: Susanne-Bunnenberg-Stiftung of the Düsseldorf Heart Center (to MK), the COSTaction BM1005 (European Network on Gasotransmitters), the FP7 Marie Curie International Reintegration program (PIRG08-GA-2010-277006, to PN) and the Faculty of Medicine, University of Southampton (to MF).Collections
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