title: Intragastric nitration by dietary nitrite: implications for modulation of protein and lipid signaling.
abstract: Inorganic nitrite, derived from the reduction of nitrate in saliva, has recently emerged as a protagonist in nitric oxide ((•)NO) biology as it can be univalently reduced to (•)NO, in the healthy human stomach. Important physiological implications have been attributed to nitrite-derived (•)NO in the gastrointestinal tract, namely modulation of host defense, blood flow, mucus formation and motility. At acidic pH, nitrite generates different nitrogen oxides depending on the local microenvironment (redox status, gastric content, pH, inflammatory conditions), including (•)NO, nitrogen dioxide ((•)NO(2)), dinitrogen trioxide (N(2)O(3)), and peroxynitrite. Thus, the gastric environment is a significant source of nitrating and nitrosating agents, especially in individuals consuming a nitrate/nitrite-rich diet on a daily basis. Both, the gastric lumen and mucosa contain putative targets for nitration, not only proteins and lipids from ingested aliments but also endogenous proteins secreted by the oxyntic glands. The physiological and functional consequences of nitration of gastric mediators will impact on local processes including food digestion and ulcerogenesis. Additionally, gastric nitration products (such as nitrated lipids) may be absorbed and affect systemic pathways. Thus, dietary ingestion of nitrate will have direct consequences for endogenous protein nitration, as indicated by our preliminary data.
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus. Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Bárbara S
authors.initials: BS
authors.lastname: Rocha
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus. Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Health Science Department, University of Aveiro.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gago
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus. Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay; Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus. Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D005502:Food; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010539:Permeability; D011499:Protein Processing, Post-Translational; D012463:Saliva / Q000378:metabolism; D013270:Stomach / Q000166:cytology
chemical_list: D009573:Nitrites; D002245:Carbon Dioxide; D009569:Nitric Oxide