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.
Bryan
Nathan S
NS
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Fernandez
Bernadette O
BO
Bauer
Selena M
SM
Garcia-Saura
Maria Francisca
MF
Milsom
Alexandra B
AB
Rassaf
Tienush
T
Maloney
Ronald E
RE
Bharti
Ajit
A
Rodriguez
Juan
J
Feelisch
Martin
M
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism* / Q000494:pharmacology; D015538:Nitrosation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D009573:Nitrites; D003577:Cytochrome P-450 Enzyme System; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1