Thesis defense Manon Denis

O-GlcNAcylation is a post-translational modification linked to metabolism and involved in the stress response and cell survival. Acute stimulation of O­GlcNAcylation is beneficial in various inflammatory response situations in adult rats. The young, who are rarely studied, are more concerned by these situations, and pathophysiology and metabolism evolve during development, which could have an impact on the response to treatment. Firstly, 1 studied the impact of age on O-GlcNAcylation levels and the expression of key enzymes in different organs at different ages in rats. The results show that O-GlcNAcylation levels are higher in young rats. ln order to assess the impact of these differences on the stress response in several situations of cardiac failure associated inflammatory response, 1 studied the effect of increased O-GlcNAcylation levels in a young rat model of septic shock (just after weaning). 1 also set up biocollections of human blood and cardiac tissue in healthy children, in septic shock and during extracorporeal circulation. We have shown that NButGT îs assocîated with an improvement in organ dysfunctîon and an increase in survival. An O-GlcNAcylomics approach in various situations has enabled us to identify O-GlcNAcylated proteins of interest, including ATP citrate lyase and carbonic anhydrase. The study of this post-translational modification in the peri-natal period and the identification of beneficial mechanisms associated with the stimulation of O-GlcNAcylation constitute major advances.