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Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues

Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues
Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues
Mammalian tissues produce nitric oxide (NO) to modify proteins at heme and sulfhydryl sites, thereby regulating vital cell functions. The majority of NO produced is widely assumed to be neutralized into supposedly inert oxidation products including nitrite (NO2(-)). Here we show that nitrite, also ubiquitous in dietary sources, is remarkably efficient at modifying the same protein sites, and that physiological nitrite concentrations account for the basal levels of these modifications in vivo. We further find that nitrite readily affects cyclic GMP production, cytochrome P450 activities, and heat shock protein 70 and heme oxygenase-1 expression in a variety of tissues. These cellular activities of nitrite, combined with its stability and abundance in vivo, suggest that this anion has a distinct and important signaling role in mammalian biology, perhaps by serving as an endocrine messenger and synchronizing agent. Thus, nitrite homeostasis may be of great importance to NO biology.
animals, cytochrome p.450 enzyme system, cytochrome p.450 enzyme system metabolism, gene expression regulation, gene expression regulation drug effects, gene expression regulation physiology, heme oxygenase 1, heme oxygenase 1 metabolism, hsp70 heat shock proteins, hsp70 heat shock proteins metabolism, humans, membrane proteins, membrane proteins metabolism, nitrites, nitrites metabolism, nitrites pharmacology, nitrosation, post translational, protein processing, signal transduction, signal transduction drug effects, signal transduction physiology
1552-4450
290-297
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Bauer, Selena M.
64194e7e-cc5f-4e98-aebb-36b32e3c34ae
Garcia-Saura, Maria Francisca
f8c30d3b-c0d5-4d1c-9280-96aca7072eb3
Milsom, Alexandra B.
7a3c8b7d-d65a-46b4-9686-1208c539253b
Rassaf, Tienush
a820a375-219a-4fa2-ae10-e77f4b1eb37c
Maloney, Ronald E.
ce656859-d89f-4fd3-93db-6c26f23fb7f4
Bharti, Ajit
77ea136c-d6fa-4da4-b26c-2687df2be981
Rodriguez, Juan
055ad15f-3cf3-4366-a11c-9a313cf2fa60
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Bryan, Nathan S.
709ff51c-c864-4862-9e3f-c5cfd3961025
Fernandez, Bernadette O.
27babc73-7646-4908-86e2-6c29d79fb938
Bauer, Selena M.
64194e7e-cc5f-4e98-aebb-36b32e3c34ae
Garcia-Saura, Maria Francisca
f8c30d3b-c0d5-4d1c-9280-96aca7072eb3
Milsom, Alexandra B.
7a3c8b7d-d65a-46b4-9686-1208c539253b
Rassaf, Tienush
a820a375-219a-4fa2-ae10-e77f4b1eb37c
Maloney, Ronald E.
ce656859-d89f-4fd3-93db-6c26f23fb7f4
Bharti, Ajit
77ea136c-d6fa-4da4-b26c-2687df2be981
Rodriguez, Juan
055ad15f-3cf3-4366-a11c-9a313cf2fa60
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Bryan, Nathan S., Fernandez, Bernadette O., Bauer, Selena M., Garcia-Saura, Maria Francisca, Milsom, Alexandra B., Rassaf, Tienush, Maloney, Ronald E., Bharti, Ajit, Rodriguez, Juan and Feelisch, Martin (2005) Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nature Chemical Biology, 1 (5), 290-297. (doi:10.1038/nchembio734). (PMID:16408049)

Record type: Article

Abstract

Mammalian tissues produce nitric oxide (NO) to modify proteins at heme and sulfhydryl sites, thereby regulating vital cell functions. The majority of NO produced is widely assumed to be neutralized into supposedly inert oxidation products including nitrite (NO2(-)). Here we show that nitrite, also ubiquitous in dietary sources, is remarkably efficient at modifying the same protein sites, and that physiological nitrite concentrations account for the basal levels of these modifications in vivo. We further find that nitrite readily affects cyclic GMP production, cytochrome P450 activities, and heat shock protein 70 and heme oxygenase-1 expression in a variety of tissues. These cellular activities of nitrite, combined with its stability and abundance in vivo, suggest that this anion has a distinct and important signaling role in mammalian biology, perhaps by serving as an endocrine messenger and synchronizing agent. Thus, nitrite homeostasis may be of great importance to NO biology.

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More information

Published date: October 2005
Keywords: animals, cytochrome p.450 enzyme system, cytochrome p.450 enzyme system metabolism, gene expression regulation, gene expression regulation drug effects, gene expression regulation physiology, heme oxygenase 1, heme oxygenase 1 metabolism, hsp70 heat shock proteins, hsp70 heat shock proteins metabolism, humans, membrane proteins, membrane proteins metabolism, nitrites, nitrites metabolism, nitrites pharmacology, nitrosation, post translational, protein processing, signal transduction, signal transduction drug effects, signal transduction physiology
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337838
URI: http://eprints.soton.ac.uk/id/eprint/337838
ISSN: 1552-4450
PURE UUID: 430647b9-f37f-4fa7-87d4-de7046de738a
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 06 Jun 2012 11:53
Last modified: 20 Jul 2019 00:42

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Contributors

Author: Nathan S. Bryan
Author: Bernadette O. Fernandez
Author: Selena M. Bauer
Author: Maria Francisca Garcia-Saura
Author: Alexandra B. Milsom
Author: Tienush Rassaf
Author: Ronald E. Maloney
Author: Ajit Bharti
Author: Juan Rodriguez
Author: Martin Feelisch ORCID iD

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