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Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo

Bryan, Nathan S., Rassaf, Tienush, Maloney, Ronald E., Rodriguez, Cynthia M., Saijo, Fumito, Rodriguez, Juan R. and Feelisch, Martin (2004) Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo Proceedings of the National Academy of Sciences, 101, (12), pp. 4308-4313. (doi:10.1073/pnas.0306706101). (PMID:15014175).

Record type: Article


There is mounting evidence that the established paradigm of nitric oxide (NO) biochemistry, from formation through NO synthases, over interaction with soluble guanylyl cyclase, to eventual disposal as nitrite/nitrate, represents only part of a richer chemistry through which NO elicits biological signaling. Additional pathways have been suggested that include interaction of NO-derived metabolites with thiols and metals to form S-nitrosothiols (RSNOs) and metal nitrosyls. Despite the overwhelming attention paid in this regard to RSNOs, little is known about the stability of these species, their significance outside the circulation, and whether other nitros(yl)ation products are of equal importance. We here show that N-nitrosation and heme-nitrosylation are indeed as ubiquitous as S-nitrosation in vivo and that the products of these reactions are constitutively present throughout the organ system. Our study further reveals that all NO-derived products are highly dynamic, have fairly short lifetimes, and are linked to tissue oxygenation and redox state. Experimental evidence further suggests that nitroso formation occurs substantially by means of oxidative nitrosylation rather than NO autoxidation, explaining why S-nitrosation can compete effectively with nitrosylation. Moreover, tissue nitrite can serve as a significant extravascular pool of NO during brief periods of hypoxia, and tissue nitrate/nitrite ratios can serve as indicators of the balance between local oxidative and nitrosative stress. These findings vastly expand our understanding of the fate of NO in vivo and provide a framework for further exploration of the significance of nitrosative events in redox sensing and signaling. The findings also raise the intriguing possibility that N-nitrosation is directly involved in the modulation of protein function.

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Published date: 23 March 2004
Keywords: nitrosothiols, nitrosamines, heme-nitrosyls, ascorbate, oxidative stress
Organisations: Clinical & Experimental Sciences


Local EPrints ID: 337846
ISSN: 0027-8424
PURE UUID: d3e2b669-b6e3-4c5c-bdc3-a31de5ff41be
ORCID for Martin Feelisch: ORCID iD

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Date deposited: 22 Jun 2012 09:15
Last modified: 18 Jul 2017 06:00

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Author: Nathan S. Bryan
Author: Tienush Rassaf
Author: Ronald E. Maloney
Author: Cynthia M. Rodriguez
Author: Fumito Saijo
Author: Juan R. Rodriguez
Author: Martin Feelisch ORCID iD

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