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Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo

Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo
Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo
There is growing evidence for the involvement of nitric oxide (NO) -mediated nitrosation in cell signaling and pathology. Although S-nitrosothiols (RSNOs) have been frequently implicated in these processes, it is unclear whether NO forms nitrosyl adducts with moieties other than thiols. A major obstacle in assessing the significance of formation of nitrosated species is the limited reliability of available analytical techniques for measurements in complex biological matrices. Here we report on the presence of nitrosated compounds in plasma and erythrocytes of rats, mice, guinea pigs, and monkeys under basal conditions, in immunologically challenged murine macrophages in vitro and laboratory animals in vivo. Besides RSNOs, all biological samples also contained mercury-stable nitroso species, indicating the additional involvement of amine and heme nitros(yl)ation reactions. Significant differences in the amounts and ratios of RSNOs over N- and heme-nitros(yl)ated compounds were found between species and organs. These observations were made possible by the development of a novel gas-phase chemiluminescence-based technique that allows detection of nitroso species in tissues and biological fluids without prior extraction or deproteinization. The method can quantify as little as 100 fmol bound NO and has been validated extensively for use in different biological matrices. Discrimination between nitrite, RSNOs, and N-nitroso or nitrosylheme compounds is accomplished by use of group-specific reagents. Our findings suggest that NO generation in vivo leads to concomitant formation of RSNOs, nitrosamines, and nitrosylhemes with considerable variation between rodents and primates, highlighting the difficulty in comparing data between different animal models and extrapolating results from experimental animals to human physiology.
nitrosothiols, nitrosamines, nitrosylheme, inflammation, plasma, red blood cells
0892-6638
1775-1785
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Rassaf, Tienush
a820a375-219a-4fa2-ae10-e77f4b1eb37c
Mnaimneh, Sanie
093bbf8e-515d-48d0-941f-271103d6eff8
Singh, Nisha
cf2bc6b0-8d3d-44c8-98e6-05005334112a
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Jourd'Heuil, David
078be18b-fa42-4a9c-a896-f64c7271bfba
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Rassaf, Tienush
a820a375-219a-4fa2-ae10-e77f4b1eb37c
Mnaimneh, Sanie
093bbf8e-515d-48d0-941f-271103d6eff8
Singh, Nisha
cf2bc6b0-8d3d-44c8-98e6-05005334112a
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Jourd'Heuil, David
078be18b-fa42-4a9c-a896-f64c7271bfba
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42

Feelisch, Martin, Rassaf, Tienush, Mnaimneh, Sanie, Singh, Nisha, Bryan, Nathan S., Jourd'Heuil, David and Kelm, Malte (2002) Concomitant S-, N-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo. The FASEB Journal, 16 (13), 1775-1785. (doi:10.1096/fj.02-0363com). (PMID:12409320)

Record type: Article

Abstract

There is growing evidence for the involvement of nitric oxide (NO) -mediated nitrosation in cell signaling and pathology. Although S-nitrosothiols (RSNOs) have been frequently implicated in these processes, it is unclear whether NO forms nitrosyl adducts with moieties other than thiols. A major obstacle in assessing the significance of formation of nitrosated species is the limited reliability of available analytical techniques for measurements in complex biological matrices. Here we report on the presence of nitrosated compounds in plasma and erythrocytes of rats, mice, guinea pigs, and monkeys under basal conditions, in immunologically challenged murine macrophages in vitro and laboratory animals in vivo. Besides RSNOs, all biological samples also contained mercury-stable nitroso species, indicating the additional involvement of amine and heme nitros(yl)ation reactions. Significant differences in the amounts and ratios of RSNOs over N- and heme-nitros(yl)ated compounds were found between species and organs. These observations were made possible by the development of a novel gas-phase chemiluminescence-based technique that allows detection of nitroso species in tissues and biological fluids without prior extraction or deproteinization. The method can quantify as little as 100 fmol bound NO and has been validated extensively for use in different biological matrices. Discrimination between nitrite, RSNOs, and N-nitroso or nitrosylheme compounds is accomplished by use of group-specific reagents. Our findings suggest that NO generation in vivo leads to concomitant formation of RSNOs, nitrosamines, and nitrosylhemes with considerable variation between rodents and primates, highlighting the difficulty in comparing data between different animal models and extrapolating results from experimental animals to human physiology.

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More information

Published date: 1 November 2002
Keywords: nitrosothiols, nitrosamines, nitrosylheme, inflammation, plasma, red blood cells
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337863
URI: http://eprints.soton.ac.uk/id/eprint/337863
ISSN: 0892-6638
PURE UUID: 59b8a144-7984-4279-9cf4-149b007c47c3
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 22 Jun 2012 12:50
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Martin Feelisch ORCID iD
Author: Tienush Rassaf
Author: Sanie Mnaimneh
Author: Nisha Singh
Author: Nathan S. Bryan
Author: David Jourd'Heuil
Author: Malte Kelm

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