An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

Sepsis in the young population, which is particularly at risk, is rarely studied. <i>O</i>-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. <i>O</i>-GlcNAc stimulation is beneficial in adult septic rats. T...

Full description

Bibliographic Details
Main Authors: Manon Denis, Thomas Dupas, Antoine Persello, Justine Dontaine, Laurent Bultot, Charlotte Betus, Thomas Pelé, Justine Dhot, Angélique Erraud, Anaïs Maillard, Jérôme Montnach, Aurélia A. Leroux, Edith Bigot-Corbel, Didier Vertommen, Matthieu Rivière, Jacques Lebreton, Arnaud Tessier, Michel De Waard, Luc Bertrand, Bertrand Rozec, Benjamin Lauzier
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
<i>O</i>-GlcNAcylation
septic shock
children
mass spectrometry
<i>O</i>-GlcNAcylomics
Online Access:https://www.mdpi.com/1422-0067/22/17/9236
id doaj-e9d2fb6c73e4487a8654807b03076041
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Manon Denis
Thomas Dupas
Antoine Persello
Justine Dontaine
Laurent Bultot
Charlotte Betus
Thomas Pelé
Justine Dhot
Angélique Erraud
Anaïs Maillard
Jérôme Montnach
Aurélia A. Leroux
Edith Bigot-Corbel
Didier Vertommen
Matthieu Rivière
Jacques Lebreton
Arnaud Tessier
Michel De Waard
Luc Bertrand
Bertrand Rozec
Benjamin Lauzier
spellingShingle Manon Denis
Thomas Dupas
Antoine Persello
Justine Dontaine
Laurent Bultot
Charlotte Betus
Thomas Pelé
Justine Dhot
Angélique Erraud
Anaïs Maillard
Jérôme Montnach
Aurélia A. Leroux
Edith Bigot-Corbel
Didier Vertommen
Matthieu Rivière
Jacques Lebreton
Arnaud Tessier
Michel De Waard
Luc Bertrand
Bertrand Rozec
Benjamin Lauzier
An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
International Journal of Molecular Sciences
<i>O</i>-GlcNAcylation
septic shock
children
mass spectrometry
<i>O</i>-GlcNAcylomics
author_facet Manon Denis
Thomas Dupas
Antoine Persello
Justine Dontaine
Laurent Bultot
Charlotte Betus
Thomas Pelé
Justine Dhot
Angélique Erraud
Anaïs Maillard
Jérôme Montnach
Aurélia A. Leroux
Edith Bigot-Corbel
Didier Vertommen
Matthieu Rivière
Jacques Lebreton
Arnaud Tessier
Michel De Waard
Luc Bertrand
Bertrand Rozec
Benjamin Lauzier
author_sort Manon Denis
title An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
title_short An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
title_full An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
title_fullStr An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
title_full_unstemmed An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat
title_sort <i>o</i>-glcnacylomic approach reveals acly as a potential target in sepsis in the young rat
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-08-01
description Sepsis in the young population, which is particularly at risk, is rarely studied. <i>O</i>-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. <i>O</i>-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of <i>O</i>-GlcNAc stimulation in young septic rats. The aim is to evaluate whether <i>O</i>-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (<i>E. Coli</i> O111:B4, 20 mg·kg<sup>−1</sup>) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg<sup>−1</sup>) ± NButGT (10 mg·kg<sup>−1</sup>) to increase <i>O</i>-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac <i>O</i>-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (<i>p</i> < 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (<i>p</i> < 0.05). ATP citrate lyase was identified among the <i>O</i>-GlcNAcylated proteins. In conclusion, <i>O</i>-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified <i>O</i>-GlcNAcylated proteins are mainly involved in cellular metabolism.
topic <i>O</i>-GlcNAcylation
septic shock
children
mass spectrometry
<i>O</i>-GlcNAcylomics
url https://www.mdpi.com/1422-0067/22/17/9236
work_keys_str_mv AT manondenis anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT thomasdupas anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT antoinepersello anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT justinedontaine anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT laurentbultot anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT charlottebetus anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT thomaspele anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT justinedhot anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT angeliqueerraud anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT anaismaillard anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT jeromemontnach anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT aureliaaleroux anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT edithbigotcorbel anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT didiervertommen anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT matthieuriviere anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT jacqueslebreton anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT arnaudtessier anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT micheldewaard anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT lucbertrand anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT bertrandrozec anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT benjaminlauzier anioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT manondenis ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT thomasdupas ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT antoinepersello ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT justinedontaine ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT laurentbultot ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT charlottebetus ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT thomaspele ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT justinedhot ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT angeliqueerraud ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT anaismaillard ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT jeromemontnach ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT aureliaaleroux ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT edithbigotcorbel ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT didiervertommen ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT matthieuriviere ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT jacqueslebreton ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT arnaudtessier ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT micheldewaard ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT lucbertrand ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT bertrandrozec ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
AT benjaminlauzier ioiglcnacylomicapproachrevealsaclyasapotentialtargetinsepsisintheyoungrat
_version_ 1717760243807551488
spelling doaj-e9d2fb6c73e4487a8654807b030760412021-09-09T13:47:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01229236923610.3390/ijms22179236An <i>O</i>-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young RatManon Denis0Thomas Dupas1Antoine Persello2Justine Dontaine3Laurent Bultot4Charlotte Betus5Thomas Pelé6Justine Dhot7Angélique Erraud8Anaïs Maillard9Jérôme Montnach10Aurélia A. Leroux11Edith Bigot-Corbel12Didier Vertommen13Matthieu Rivière14Jacques Lebreton15Arnaud Tessier16Michel De Waard17Luc Bertrand18Bertrand Rozec19Benjamin Lauzier20Université de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pôle of Cardiovascular Research, B-1200 Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pôle of Cardiovascular Research, B-1200 Brussels, BelgiumUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceDepartement of Biochemistry, CHU de Nantes, F-44000 Nantes, FranceUniversité Catholique de Louvain, de Duve Institute, Mass Spectrometry Platform, B-1200 Brussels, BelgiumUniversité de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Faculté des Sciences et des Techniques, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Faculté des Sciences et des Techniques, F-44000 Nantes, FranceUniversité de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Faculté des Sciences et des Techniques, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pôle of Cardiovascular Research, B-1200 Brussels, BelgiumUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceUniversité de Nantes, CHU Nantes, CNRS, INSERM, l’Institut du Thorax, F-44000 Nantes, FranceSepsis in the young population, which is particularly at risk, is rarely studied. <i>O</i>-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. <i>O</i>-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of <i>O</i>-GlcNAc stimulation in young septic rats. The aim is to evaluate whether <i>O</i>-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (<i>E. Coli</i> O111:B4, 20 mg·kg<sup>−1</sup>) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg<sup>−1</sup>) ± NButGT (10 mg·kg<sup>−1</sup>) to increase <i>O</i>-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac <i>O</i>-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (<i>p</i> < 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (<i>p</i> < 0.05). ATP citrate lyase was identified among the <i>O</i>-GlcNAcylated proteins. In conclusion, <i>O</i>-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified <i>O</i>-GlcNAcylated proteins are mainly involved in cellular metabolism.https://www.mdpi.com/1422-0067/22/17/9236<i>O</i>-GlcNAcylationseptic shockchildrenmass spectrometry<i>O</i>-GlcNAcylomics

Similar Items