1. O-GlcNAc stimulation: A new metabolic approach to treat septic shock
- Author
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Ferron, Marine, Cadiet, julien, Persello, Antoine, Prat, Valentine, Denis, Manon, Erraud, Angélique, Aillerie, Virginie, Mével, Mathieu, Bigot, Edith, Chatham, John, Gauthier, Chantal, Rozec, Bertrand, Lauzier, Benjamin, JAULIN, Nicolas, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes), Division of Molecular and Cellular Pathology [Birmingham], and unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX)
- Subjects
Lipopolysaccharides ,Male ,[SDV]Life Sciences [q-bio] ,lcsh:R ,lcsh:Medicine ,Bridged Bicyclo Compounds, Heterocyclic ,Shock, Septic ,beta-N-Acetylhexosaminidases ,Article ,Acetylglucosamine ,Rats ,Sarcoplasmic Reticulum Calcium-Transporting ATPases ,[SDV] Life Sciences [q-bio] ,Disease Models, Animal ,Animals ,Fluid Therapy ,Humans ,lcsh:Q ,Bacterial infection ,lcsh:Science ,Protein Processing, Post-Translational ,Cardiac device therapy - Abstract
International audience; Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. Increases in O-GlcNAcylation have shown beneficial cardiovascular effects in acute pathologies. We used two different rat models to evaluate the beneficial effects of O-GlcNAc stimulation at the early phase of septic shock. Rats received lipopolysaccharide (LPS) to induce endotoxemic shock or saline (control) and fluid resuscitation (R) with or without O-GlcNAc stimulation (NButGT-10 mg/kg) 1 hour after shock induction. For the second model, rats received cecal ligature and puncture (CLP) surgery and fluid therapy with or without NButGT. Cardiovascular function was evaluated and heart and blood samples were collected and analysed. NButGT treatment efficiently increased total O-GlcNAc without modification of HBP enzyme expression.Treatment improved circulating parameters and cardiovascular function in both models, and restored SERCA2a expression levels. NButGT treatment also reduced animal mortality. In this study, we demonstrate that in septic shock O-GlcNAc stimulation improves global animal and cardiovascular function outcomes associated with a restoration of SERCA2a levels. This pre-clinical study opens avenues for a potential therapy of early-stage septic shock.
- Published
- 2019
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