Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide

Whiteman, Matthew; Li, Ling; Kostetski, Iouri; Chu, Siew Hwa; Siau, Jia Ling; Bhatia, Madhav; Moore, Philip K.

doi:10.1016/j.bbrc.2006.02.154

Cited by 354 publications

(289 citation statements)

References 33 publications

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“…The recent surge of interest in this chemistry in the biological community (13)(14)(15) was triggered by a growing appreciation that NO and sulfide exert similar and often interdependent biological actions within the cardiovascular system and elsewhere (NO/H 2 S "cross-talk") (16,17), resulting in mutual attenuation or potentiation of their responses. This crosstalk is possibly mediated by chemical interactions (18)(19)(20), but much of the older chemical work seems to have been forgotten. Recently, low concentrations of sulfide were shown to quench NO-mediated vascular responses through formation of an uncharacterized "nitrosothiol" (RSNO) (18)(19)(20), assumed to be thionitrous acid (HSNO) (13)(14)(15).…”

Section: Significancementioning

confidence: 99%

“…This crosstalk is possibly mediated by chemical interactions (18)(19)(20), but much of the older chemical work seems to have been forgotten. Recently, low concentrations of sulfide were shown to quench NO-mediated vascular responses through formation of an uncharacterized "nitrosothiol" (RSNO) (18)(19)(20), assumed to be thionitrous acid (HSNO) (13)(14)(15).…”

Section: Significancementioning

confidence: 99%

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Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Cortese‐Krott

Kuhnle

Dyson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

253

280

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Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H 2 S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H 2 S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO − ), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO − is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO − synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N 2 O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H 2 S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.sulfide | nitric oxide | nitroxyl | redox | gasotransmitter N itrogen and sulfur are essential for all known forms of life on Earth. Our planet's earliest atmosphere is likely to have contained only traces of O 2 but rather large amounts of hydrogen sulfide (H 2 S) (1). Indeed, sulfide may have supported life long before the emergence of O 2 and NO (2, 3).* This notion is consistent with a number of observations: H 2 S is essential for efficient abiotic amino acid generation as evidenced by the recent reanalysis of samples of Stanley Miller's original spark discharge experiments (4), sulfide is an efficient reductant in protometabolic reactions forming RNA, protein, and lipid precursors (5), and sulfide is both a bacterial and mitochondrial substrate (6), enabling even multicellular lifeforms to exist and reproduce under conditions of permanent anoxia (7). Thus, although eukaryotic cells may have originated from the symbiosis of sulfurreducing and -oxidizing lifeforms within a self-contained sulfur redox metabolome (8), sulfide may have been essential even earlier by providing the basic building blocks of ...

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Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Cortese‐Krott

Kuhnle

Dyson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

253

280

View full text Add to dashboard Cite

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“…Similarly, H2S can be stored in the form of sulfane sulfur and transported and released in response to a physiological stimulus [3]. A number of publications reported on the molecular interaction between H2S and NO or NO-donors [4][5][6][7][8][9][10][11][12][13][14], and H2S and NO were found to cooperatively regulate vascular tone by activating a neuroendocrine signaling pathway in which formation of nitroxyl (HNO) appears to play an important role [13]. Products of this H2S/NO interaction appear to have pronounced biological effects; however the nature of the reaction intermediates is currently unclear and many inconsistencies remain; for example, H2S donors were found to either potentiate or attenuate relaxation effect of NO donors in isolated aortic rings in vitro [15,16], or result in complete loss of vasodepressor activity in anesthetized rats [16].…”

Section: Introductionmentioning

confidence: 99%

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

et al. 2015

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A B S T R A C TThe chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO -) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50 nM), whereas Na2S and polysulfides have little effect at 1-5 μM. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500 nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10 μM), and by the NO scavenger cPTIO (100 μM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1 mM) or methemoglobin (20 μM heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500 nM based on the starting material) was inhibited to a lesser extent by ODQ, only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD2)-Fe 2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO -, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk.

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“…23 H 2 S has been shown to both enhance 14 and attenuate 7 the relaxant effect of NO in the rat aorta, whilst NO has been shown to enhance the release of H 2 S in rat vascular tissues and increase the expression of CSE in cultured vascular smooth muscle cells. 15 There is evidence that NO and peroxynitrite react with H 2 S to form a novel nitrosothiol, which has been proposed to regulate the physiological effects of both NO and H 2 S. 24 In homogenates of rat aorta, NO donors increased CSE-dependent H 2 S generation in a cGMP-dependent manner. 21 Prolonged incubation of cultured vascular smooth muscle cells with NO donors produced an increase in the CSE mRNA and protein levels.…”

Section: H 2 S Interaction With Nomentioning

confidence: 99%

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)

Elsey

Fowkes

Baxter

2010

Cell Biochemistry & Function

138

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Since the discovery of endogenously-produced hydrogen sulfide (H 2 S) in various tissues, there has been an explosion of interest in H 2 S as a biological mediator alongside other gaseous mediators, nitric oxide and carbon monoxide. The identification of enzymeregulated H 2 S synthetic pathways in the cardiovascular system has led to a number of studies examining specific regulatory actions of H 2 S. We review evidence showing that endogenously-generated and exogenously-administered H 2 S exerts a wide range of actions in vascular and myocardial cells including vasodilator/vasoconstrictor effects via modification of the smooth muscle tone, induction of apoptosis and anti-proliferative responses in the smooth muscle cells, angiogenic actions, effects relevant to inflammation and shock, and cytoprotection in models of myocardial ischemia-reperfusion injury. Several molecular mechanisms of action of H 2 S have been described. These include interactions of H 2 S with NO, redox regulation of multiple signaling proteins and regulation of K ATP channel opening. The gaps in our current understanding of precise mechanisms, the absence of selective pharmacological tools and the limited availability of H 2 S measurement techniques for living tissues, leave many questions about physiological and pathophysiological roles of H 2 S unanswered at present. Nevertheless, this area of investigation is advancing rapidly. We believe H 2 S holds promise as an endogenous mediator controlling a wide range of cardiovascular cell functions and integrated responses under both physiological and pathological conditions and may be amenable to therapeutic manipulation.

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Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide

Cited by 354 publications

References 33 publications

Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)

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Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide

Cited by 354 publications

References 33 publications

Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

Regulation of cardiovascular cell function by hydrogen sulfide (H2S)

Contact Info

Product

Resources

About

Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Key bioactive reaction products of the NO/H₂S interaction are S/N-hybrid species, polysulfides, and nitroxyl

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)