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N-Nitroso products from the reaction of indoles with Angeli's salt

N-Nitroso products from the reaction of indoles with Angeli's salt
N-Nitroso products from the reaction of indoles with Angeli's salt
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-l-tryptophan) 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, N-nitrosoindole formation appears to proceed via a mechanism that involves electrophilic attack of HNO 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.
0893-228X
58-67
Peyrot, Fabienne
914bfbb7-e524-48cf-8037-57aed21ae7f3
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Bryan, Nathan S
1983aefc-d955-4e40-9463-07b24128e5ea
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Ducrocq, Claire
04cd2cea-6b8f-46c3-9c02-e70e06a9ed15
Peyrot, Fabienne
914bfbb7-e524-48cf-8037-57aed21ae7f3
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Bryan, Nathan S
1983aefc-d955-4e40-9463-07b24128e5ea
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Ducrocq, Claire
04cd2cea-6b8f-46c3-9c02-e70e06a9ed15

Peyrot, Fabienne, Fernandez, Bernadette O., Bryan, Nathan S, Feelisch, Martin and Ducrocq, Claire (2006) N-Nitroso products from the reaction of indoles with Angeli's salt. Chemical Research in Toxicology, 19 (1), 58-67. (doi:10.1021/tx050253b). (PMID:16411657)

Record type: Article

Abstract

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-l-tryptophan) 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, N-nitrosoindole formation appears to proceed via a mechanism that involves electrophilic attack of HNO 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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2005 Peyrot - CRT-N-nitroso-Indoles-final revised.pdf-for eprint.pdf - Other
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e-pub ahead of print date: 9 December 2005
Published date: January 2006
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337836
URI: http://eprints.soton.ac.uk/id/eprint/337836
ISSN: 0893-228X
PURE UUID: 1426775c-2ba9-478c-b7d5-7998b28d677c
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 06 Jun 2012 10:35
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Fabienne Peyrot
Author: Bernadette O. Fernandez
Author: Nathan S Bryan
Author: Martin Feelisch ORCID iD
Author: Claire Ducrocq

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