title: Glutamine enema regulates colonic ubiquitinated proteins but not proteasome activities during TNBS-induced colitis leading to increased mitochondrial activity.
abstract: Ubiquitin proteasome system contributes to the regulation of intestinal inflammatory response as its inhibition is associated with tissue damage improvement. We aimed to evaluate whether glutamine is able to limit inflammation by targeting ubiquitin proteasome system in experimental colitis. Colitis was induced in male rats by intrarectal instillation of 2-4-6-trinitrobenzen sulfonic acid (TNBS) at day 1. From day 2 to day 6, rats daily received either an intrarectal instillation of PBS (TNBS/PBS group) or glutamine (TNBS/Gln). Rats were euthanized at day 7 and colonic samples were taken to evaluate ubiqutinated proteins by proteomic approach combining 2D electrophoresis and immunoblots directed against ubiquitin. Results were then confirmed by evaluating total expression of proteins and mRNA levels. Survival rate, TNFα, and IL-1β mRNA were improved in TNBS/Gln compared with TNBS/PBS (p < 0.05). Proteasome activities were affected by TNBS but not by glutamine. We identified eight proteins that were less ubiquitinated in TNBS/PBS compared with controls with no effect of glutamine. Four proteins were more ubiquitinated in TNBS/PBS group and restored in TNBS/Gln group. Finally, 12 ubiquitinated proteins were only affected by glutamine. Among proteins affected by glutamine, eight proteins (GFPT1, Gapdh, Pkm2, LDH, Bcat2, ATP5a1, Vdac1, and Vdac2) were involved in metabolic pathways. In conclusion, glutamine may regulate ubiquitination process during intestinal inflammation.
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bertrand
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marion-Letellier
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Saïda
authors.initials: S
authors.lastname: Azhar
authors.affiliation: Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.|Plateform of Proteomics PISSARO, Mont-Saint-Aignan, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Legrand
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Goichon
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Ghouzali
authors.affiliation: Laboratory of Anatomo-Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Moutaz
authors.initials: M
authors.lastname: Aziz
authors.affiliation: Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.|Plateform of Proteomics PISSARO, Mont-Saint-Aignan, France.|INSERM Unit 982, Mont-Saint-Aignan, France.
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Savoye
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.|Department of Nutrition, Rouen University Hospital, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: INSERM Unit 1073, Nutrition Inflammation and Gut Brain Axis, Rouen, France.|Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, France.|Department of Nutrition, Rouen University Hospital, Rouen, France.
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D003092:Colitis / Q000378:metabolism*; D004733:Enema; D005973:Glutamine / Q000627:therapeutic use*; D047468:Immunoprecipitation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D054875:Ubiquitination
chemical_list: D005973:Glutamine
keywords: Cell biology; Colitis; Colon; Glutamine; Proteasome; Rat; Ubiquitin