Differential actions of L‐cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta

Ellis, Anthie; Li, Chun Guang; Rand, M. J.

doi:10.1038/sj.bjp.0703058

Cited by 90 publications

(108 citation statements)

References 41 publications

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“…Endogenous and exogenous thiols are often used in studies involving • NO and/or H 2 S signaling pathways (Stamler 1994;Ellis et al 2000;Gaston et al 2006;Duan and Chen 2007;Li et al 2009;Yong et al 2010Yong et al , 2011Kasparek et al 2012). Our results may suggest that in these studies, a possible modulation of H 2 S-induced…”

Section: Biological Significancementioning

confidence: 57%

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Low molecular thiols, pH and O2 modulate H2S-induced S-nitrosoglutathione decomposition – •NO release

Grman

Misak²,

Jacob³

et al. 2014

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Abstract.We studied the involvement of O 2 , pH and low molecular thiols in H 2 S-induced decomposition of S-nitrosoglutathione (GSNO). The GSNO decomposition -• NO release was evaluated by UV-VIS spectroscopy and Griess assay. The H 2 S donor Na 2 S was used. O 2 slightly increased, but was not necessary for the H 2 S-induced GSNO decomposition. The rate of GSNO decomposition depended on pH; the maximum rate was observed at pH 7.4-8.0, and this decreased with lowering pH (6.4-4.5) as well as with increasing pH at 9.0-12.0. H 2 S-induced GSNO decomposition was slowed by the presence of other thiols, such as L-cysteine (Cys), N-acetyl-L-cysteine (NAC) and Lglutathione (GSH), but not in the presence of L-methionine (Met) or oxidized glutathione (GSSG). In sharp contrast, at pH 6.0, H 2 S-induced GSNO decomposition was negligible, yet the presence of Cys, NAC and GSH induced the H 2 S-driven GSNO decomposition (whilst Met and GSSG were inactive). In conclusion we postulate an involvement of low molecular thiols and pH in• NO signaling, by modulating the interactions of H 2 S with nitroso compounds, and hence in part they also appear to control H 2 S-triggered• NO release. The interaction of H 2 S and/or its derivatives with the thiol group may be responsible for the observed effects.

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Section: Biological Significancementioning

confidence: 57%

“…• NO and H 2 S signaling pathways (Stamler 1994;Ellis et al 2000;Gaston et al 2006;Duan and Chen 2007;Li et al 2009;Yong et al 2010;Yong et al 2011;Kasparek et al 2012). For instance, thiols such as Cys, NAC and GSH have been reported to influence the • NO-H 2 S effects on myocyte contraction (Yong et al 2010(Yong et al , 2011.…”

Section: Introductionmentioning

confidence: 99%

Low molecular thiols, pH and O2 modulate H2S-induced S-nitrosoglutathione decomposition – •NO release

Grman

Misak²,

Jacob³

et al. 2014

gpb

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“…Like NO ⅐ , NO Ϫ induces vasodilation in vivo and in vitro in association with the formation of iron-nitrosyl complexes and the conversion of NO Ϫ to NO ⅐ (11-13). These effects are highly sensitive to redox state, being effectively eliminated by the addition of reduced thiols (13,14) or copper-containing enzymes (15). Whether and how NO Ϫ affects the intact heart itself remains unknown, but this too might be anticipated to display marked redox sensitivity.…”

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confidence: 99%

Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling

Paolocci

Saavedra

Miranda

et al. 2001

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

289

284

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Nitroxyl anion (NO ؊ ) is the one-electron reduction product of nitric oxide (NO ⅐ ) and is enzymatically generated by NO synthase in vitro. The physiologic activity and mechanism of action of NO ؊ in vivo remains unknown. The NO ؊ generator Angeli's salt (AS, Na2N2O3) was administered to conscious chronically instrumented dogs, and pressure-dimension analysis was used to discriminate contractile from peripheral vascular responses. AS rapidly enhanced left ventricular contractility and concomitantly lowered cardiac preload volume and diastolic pressure (venodilation) without a change in arterial resistance. There were no associated changes in arterial or venous plasma cGMP. The inotropic response was similar despite reflex blockade with hexamethonium or volume reexpansion, indicating its independence from baroreflex stimulation. However, reflex activation did play a major role in the selective venodilation observed under basal conditions. These data contrasted with the pure NO donor diethylamine͞NO, which induced a negligible inotropic response and a more balanced veno͞arterial dilation. AS-induced positive inotropy, but not systemic vasodilatation, was highly redox-sensitive, being virtually inhibited by coinfusion of N-acetyl-L-cysteine. Cardiac inotropic signaling by NO ؊ was mediated by calcitonin gene-related peptide (CGRP), as treatment with the selective CGRP-receptor antagonist CGRP-(8 -37) prevented this effect but not systemic vasodilation. Thus, NO ؊ is a redox-sensitive positive inotrope with selective venodilator action, whose cardiac effects are mediated by CGRP-receptor stimulation. This fact is evidence linking NO ؊ to redox-sensitive cardiac contractile modulation by nonadrenergic͞noncholinergic peptide signaling. Given its cardiac and vascular properties, NO ؊ may prove useful for the treatment of cardiovascular diseases characterized by cardiac depression and elevated venous filling pressures.N itric oxide (NO ⅐ )-related species play a crucial role in diverse physiological processes, including blood pressure regulation, neurotransmission, and cytostatic͞cytotoxic signaling (1). Whereas some NO ⅐ -mediated cardiovascular effects are firmly established, its control over myocardial contractility remains controversial in that positive, negative, or neutral effects can be observed. The net result varies with the tissue preparation, NO ⅐ concentration and donor, and myocardial redox state (2, 3). These factors can critically influence the particular NO ⅐ species generated and, thereby, the net contractile response.Among the NO ⅐ -related species is nitroxyl anion (NO Ϫ ), the one-electron reduction product of NO ⅐ that is formed by NO ⅐ synthase in vitro by direct enzyme action or metabolism of the decoupled NO ⅐ synthase product N G -hydroxy-L-arginine (4-8). At high concentrations of 0.1-5 mM, NO Ϫ seems more cytotoxic than NO ⅐ in vitro, causing DNA strand breaks and base oxidation (9, 10). Like NO ⅐ , NO Ϫ induces vasodilation in vivo and in vitro in association with the formation of iron-nitro...

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“…It has been suggested that HNO can affect the etiology of various pathophysiological conditions such as inflammation and neurodegenerative diseases, especially when H 2 O 2 and transition metal ions are present (6,7). Similar to NO ⅐ and NO ϩ , HNO is a potent inducer of the antioxidant protein heme oxygenase 1 (8), exhibits vasorelaxant properties (9), and modulates the activity of thiol-containing proteins, such as aldehyde dehydrogenase (10,11) and the N-methyl-D-aspartate receptor (12,13). In in vivo experiments, Paolocci et al (14) observed that HNO exerts positive inotropic and lusitropic action, which unlike NO ⅐ and nitrates is independent and additive to ␤-adrenergic stimulation and increases the release of plasma calcitonin gene-related peptide; these results suggest that donors of HNO are potential prodrugs for the treatment of heart failure (14).…”

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confidence: 99%

Formation of Nitroxyl and Hydroxyl Radical in Solutions of Sodium Trioxodinitrate

Ivanova

Salama

Clancy

et al. 2003

Journal of Biological Chemistry

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Despite its negative redox potential, nitroxyl (HNO) can trigger reactions of oxidation. Mechanistically, these reactions were suggested to occur with the intermediate formation of either hydroxyl radical ( ⅐ OH) or peroxynitrite (ONOO ؊ ). In this work, we present further experimental evidence that HNO can generate ⅐ OH. Sodium trioxodinitrate (Na 2 N 2 O 3 ), a commonly used donor of HNO, oxidized phenol and Me 2 SO to benzene diols and ⅐ CH 3 , respectively. The oxidation of Me 2 SO was O 2 -independent, suggesting that this process reflected neither the intermediate formation of ONOO ؊ nor a redox cycling of transition metal ions that could initiate Fenton-like reactions. In solutions of phenol, Na 2 N 2 O 3 yielded benzene-1,2-diol and benzene-1,4-diol at a ratio of 2:1, which is consistent with the generation of free ⅐ OH. Ethanol and Me 2 SO, which are efficient scavengers of ⅐ OH, impeded the hydroxylation of phenol. A mechanism for the hydrolysis of Na 2 N 2 O 3 is proposed that includes dimerization of HNO to cis-hyponitrous acid (HO-N‫؍‬N-OH) with a concomitant azo-type homolytic fission of the latter to N 2 and ⅐ OH. The HNO-dependent production of ⅐ OH was with 1 order of magnitude higher at pH 6.0 than at pH 7.4. Hence, we hypothesized that HNO can exert selective toxicity to cells subjected to acidosis. In support of this thesis, Na 2 N 2 O 3 was markedly more toxic to human fibroblasts and SK-N-SH neuroblastoma cells at pH 6.2 than at pH 7.4. Scavengers of ⅐ OH impeded the cytotoxicity of Na 2 N 2 O 3 . These results suggest that the formation of HNO may be viewed as a toxicological event in tissues subjected to acidosis.The biochemistry of nitroxyl (HNO) has attracted considerable interest in recent years. In cells, the biosynthesis of HNO is believed to proceed via reduction of NO ⅐ by superoxide dismutase (1) and cytochrome c (2), and reduction of S-nitrosoglutathione by low molecular weight and protein thiols (3-5). It has been suggested that HNO can affect the etiology of various pathophysiological conditions such as inflammation and neurodegenerative diseases, especially when H 2 O 2 and transition metal ions are present (6, 7). Similar to NO ⅐ and NO ϩ , HNO is a potent inducer of the antioxidant protein heme oxygenase 1 (8), exhibits vasorelaxant properties (9), and modulates the activity of thiol-containing proteins, such as aldehyde dehydrogenase (10, 11) and the N-methyl-D-aspartate receptor (12, 13). In in vivo experiments, Paolocci et al. (14) observed that HNO exerts positive inotropic and lusitropic action, which unlike NO ⅐ and nitrates is independent and additive to ␤-adrenergic stimulation and increases the release of plasma calcitonin gene-related peptide; these results suggest that donors of HNO are potential prodrugs for the treatment of heart failure (14). At high doses, HNO has been shown to induce DNA singlestrand breakage (15, 16) and a concentration-dependent cytotoxicity in murine thymocytes (16). This cytotoxicity was associated with activation of the nuclear nick sen...

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Differential actions of L‐cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta

Cited by 90 publications

References 41 publications

Low molecular thiols, pH and O2 modulate H2S-induced S-nitrosoglutathione decomposition – •NO release

Low molecular thiols, pH and O2 modulate H2S-induced S-nitrosoglutathione decomposition – •NO release

Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling

Formation of Nitroxyl and Hydroxyl Radical in Solutions of Sodium Trioxodinitrate

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