Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response
2016
Beaumont, Martin | Andriamihaja, Mireille | Lan, Annaig | Khodorova, Nadezda | Audebert, Marc | Blouin, Jean-Marc | Grauso, Marta | Lancha, Luciana | Benetti, Pierre-Henri | Benamouzig, Robert | Tomé, Daniel | Bouillaud, Frédéric | Davila, Anne-Marie | Blachier, Francois | Physiologie de la Nutrition et du Comportement Alimentaire (PNCA) ; Institut National de la Recherche Agronomique (INRA)-AgroParisTech | Métabolisme et Xénobiotiques (ToxAlim-MeX) ; ToxAlim (ToxAlim) ; Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Universidade de São Paulo = University of São Paulo (USP) | Service de Gastro-entérologie [Avicenne] ; Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Fondation ARC pour la Recherche sur le cancer [20131200283] ; PRES Sorbonne Paris Cite; INRA; AgroParisTech | European Project: 613979,EC:FP7:KBBE,FP7-KBBE-2013-7-single-stage,MYNEWGUT(2013)
WOS:000371219400015
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显示更多 [+] 显示较少 [-]英语. Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1 alpha (Hif-1 alpha) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the gamma H(2)AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite. (C) 2016 Elsevier Inc. All rights reserved.
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