title: Dietary nitrite induces nitrosation of the gastric mucosa: the protective action of the mucus and the modulatory effect of red wine.
abstract: The stomach chemical environment promotes the production of new molecules that can induce post-translational modifications of endogenous proteins with physiological impact. The nitrate-nitrite-nitric oxide pathway is relevant in this process via production of nitric oxide ((•)NO) and nitric oxide-derived nitrogen oxides (NOx) at high concentrations. Using a highly sensitive and selective chemiluminescence approach, we found that exposure the stomach of rats to nitrite yielded S- and N-nitroso derivatives in gastric mucus cysteine-rich glycoproteins (mucins). To lesser extent, the underlying epithelial cell layers also suffered nitrite-driven S- and N-nitroso modifications which increased upon mucus removal, indicating that, under normal nitrite load, (•)NO and NOx can reach inner layers of the stomach wall and locally modify proteins. S-nitrosation was by large the predominant modification. In vitro and ex vivo experiments indicated that the gastric nitrosation pattern is triggered by dietary nitrite in a concentration dependent manner, encompassing the intermediary formation of (•)NO and is susceptible to modulation by dietary reductants, notably red wine polyphenols. Collectively, these results suggest a protective action of the mucus and potential (•)NO-dependent biochemical effects at deeper cells layers of the mucosa.
authors.affiliation: Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal.
authors.forename: Cassilda
authors.initials: C
authors.lastname: Pereira
authors.affiliation: Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.affiliation: Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000818:Animals; D004032:Diet; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009093:Mucus; D009573:Nitrites / Q000008:administration & dosage / Q000494:pharmacology*; D015538:Nitrosation; D051381:Rats; D017208:Rats, Wistar; D014920:Wine
chemical_list: D009573:Nitrites
keywords: Diet; Mucins; Nitric oxide; Nitrite; Nitrosation; Stomach