Induction of DNA strand breakage and base oxidation by nitroxyl anion through hydroxyl radical production

Ohshima, Hiroshi; Gilibert, Isabelle; Bianchini, Franca

doi:10.1016/s0891-5849(98)00327-x

Cited by 84 publications

(61 citation statements)

References 32 publications

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“…Furthermore, such effects are dose dependent. In this regard, the AS dose used in the present study was Ͻ10 Ϫ4 -fold lower than that used in vitro (9,10), in which cytotoxic effects were observed, and was comparable to the lowest dose used in the only prior in vivo study done in an ischemia͞reperfusion model (21).…”

Section: Discussionmentioning

confidence: 51%

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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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Section: Discussionmentioning

confidence: 51%

“…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-nitrosyl complexes and the conversion of NO Ϫ to NO ⅐ (11-13).…”

mentioning

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

View full text Add to dashboard Cite

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“…Mechanistically, these reactions were suggested to occur with the intermediate formation of [49][50][51][52][53] or (an isomer of) [54] peroxynitrite; [53,55] direct detection of the corresponding oxidizing species, however, has proven to be difficult. Irrespectively of the exact mechanism of these reaction(s), overproduction of HNO in tissues subjected to acidosis may lead to oxidative stress inasmuch as the ability of HNO to act as a pro-oxidant dramatically increases in acidic solutions (ref.…”

Section: Chemical Fate Of No• In Biological Systemsmentioning

confidence: 99%

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz¹,

Kim²,

Bagci³

et al. 2004

CMM

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“…• , nitroxyl offers both protective (7, 23) as well as proinflammatory and cytotoxic effects (24,25), depending on dose or concentration, and reaction conditions. In addition, it is a potent thiol oxidant (25).…”

Section: Nitrosothiols (17)mentioning

confidence: 99%

“…AS is known to induce relaxation of vascular smooth muscle in vitro and to lower systemic blood pressure in vivo, effects which may be associated with the formation of iron-nitrosyl complexes (28,29). Acute toxicity is often attributed to reductive nitrosylation of transition metals (30,31), thiol modification (32), and to hydroxylation of aromatic compounds (24). While it has been observed that organ protection may occur after AS administration, there is no unifying mechanism to account for such an effect.…”

Section: Nitrosothiols (17)mentioning

confidence: 99%

N-Nitroso Products from the Reaction of Indoles with Angeli's Salt

Peyrot¹,

Fernandez²,

Bryan³

et al. 2005

Chem. Res. Toxicol.

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While nitroxyl (HNO) has been shown to engage in oxidation and hydroxylation reactions, little is known about its nitrosating potential. We therefore sought to investigate the kinetics of formation and identity of the reaction products of the classical nitroxyl donor Angeli's salt (AS) with three representative tryptophan derivates (melatonin, indol-3-acetic acid, and N-acetyl-Ltryptophan) in vitro. In the presence of oxygen and at physiological pH, we find that the major products generated are the corresponding N-nitrosoindoles with negligible formation of oxidation and nitration products. A direct comparison of the effects of AS, nitrite, peroxynitrite, aqueous NO• solution and the NO-donor DEA/NO toward melatonin revealed that nitrite does not participate in the reaction and that peroxynitrite is not an intermediate. Rather, Nnitrosoindole formation appears to proceed via a mechanism that involves electrophilic attack of nitroxyl on the indole nitrogen, followed by a reaction of the intermediary hydroxylamine derivative with oxygen. Further in vivo experiments demonstrated that AS exhibits a unique nitrosation signature which differs from that of DEA/NO inasmuch as substantial amounts of a mercury-resistant nitroso species are generated in the heart whereas S-nitrosothiols are the major reaction products in plasma. These data are consistent with the notion that the generation of nitroxyl in vivo gives rise to formation of nitrosative post-translational protein modifications in the form of either S-or N-nitroso products, depending on the redox environment. It is intriguing to speculate that the particular efficiency of nitroxyl to form N-nitroso species in the heart may account for the positive inotropic effects observed with AS earlier.

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Induction of DNA strand breakage and base oxidation by nitroxyl anion through hydroxyl radical production

Cited by 84 publications

References 32 publications

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

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

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

N-Nitroso Products from the Reaction of Indoles with Angeli's Salt

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