Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

• Published in: International journal of molecular sciences Vol. 23; no. 12; p. 6430
• Main Authors: Dupas, Thomas, Persello, Antoine, Blangy-Letheule, Angélique, Denis, Manon, Erraud, Angélique, Aillerie, Virginie, Leroux, Aurélia A, Rivière, Matthieu, Lebreton, Jacques, Tessier, Arnaud, Rozec, Bertrand, Lauzier, Benjamin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-06-2022; MDPI
• Subjects: Acetylglucosamine - metabolism; Animals; Biochemistry, Molecular Biology; Cell division; Cellular stress response; Cytokines; Enzymes; Escherichia coli - metabolism; Gene Expression; Genomics; Heart; Human health and pathology; Infectious diseases; Inflammation; Injection; Life Sciences; Lipopolysaccharides; Lipopolysaccharides - metabolism; Male; MAP kinase; Metabolism; N-Acetylglucosaminyltransferases - metabolism; NF-κB protein; O-GlcNAcylation; Pharmaceutical sciences; Pharmacology; Post-translation; post-translational modification; Protein Processing, Post-Translational; Proteins; Rats; Rodents; Sepsis; Sepsis - genetics; Sepsis - therapy; Sodium chloride; Sodium Chloride - metabolism; Stimulation; therapeutic strategy; Transcription; transcriptomic; Tumor necrosis factor-TNF; O-GlcNAcylation; therapeutic strategy; post-translational modification; transcriptomic; gene expression; sepsis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23126430

The young population, which is particularly at risk of sepsis, is, paradoxically, rarely studied. Acute stimulation of O-GlcNAcylation, a post-translational modification involved in metabolic regulation, cell survival and stress response, is beneficial in young rats with sepsis. Considering that sepsis impacts the gene expression profile and that O-GlcNAcylation is a regulator of transcription, the aims of this study are to (i) unveil beneficial mechanisms of O-GlcNAcylation and (ii) decipher the relationship between O-GlcNAcylation and transcription during sepsis. Endotoxemic challenge was induced in 28-day-old male rats using a lipopolysaccharide injection (E. coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after, rats were assigned to no therapy or fluidotherapy (NaCl 0.9%, 10 mL.kg−1) ± NButGT (10 mg·kg−1) to stimulate O-GlcNAc levels. Cardiac O-GlcNAcylation levels were evaluated via Western blot and gene transcription using 3′ SRP analysis. Lipopolysaccharide injection favorizes inflammatory state with the overexpression of genes involved in the NF-κB, JAK/STAT and MAPK pathways. NButGT treatment increased cardiac O-GlcNAcylation levels (p < 0.05). Yet, the mRNA expression was not impacted two hours after fluidotherapy or NButGT treatment. In conclusion, O-GlcNAc stimulation-induced beneficial effects are not dependent on the gene expression profile at the early phase of sepsis.