Protein O‐GlcNAcylation levels are regulated independently of dietary intake in a tissue and time‐specific manner during rat postnatal development. (16th October 2020)

• Record Type: Journal Article
• Authors: Dupas, Thomas; Denis, Manon; Dontaine, Justine; Persello, Antoine; Bultot, Laurent; Erraud, Angélique; Vertommen, Didier; Bouchard, Bertrand; Tessier, Arnaud; Rivière, Matthieu; Lebreton, Jacques; Bigot‐Corbel, Edith; Montnach, Jérôme; De Waard, Michel; Gauthier, Chantal; Burelle, Yan; Olson, Aaron K.; Rozec, Bertrand; Des Rosiers, Christine; Bertrand, Luc; Issad, Tarik; Lauzier, Benjamin
• Is Part Of: Acta physiologica. Volume 231:Number 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-16
• Subjects: development -- hexosamine biosynthesis pathway -- mass spectrometry -- metabolism -- O‐GlcNAcylation -- O‐GlcNAcylomic; Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.13566
• Languages: English
• ISSNs: 1748-1708

Abstract

Abstract: Aim: Metabolic sources switch from carbohydrates in utero, to fatty acids after birth and then a mix once adults. O ‐GlcNAcylation ( O ‐GlcNAc) is a post‐translational modification considered as a nutrient sensor. The purpose of this work was to assess changes in protein O ‐GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact of O ‐GlcNAcylation on cardiac proteins. Methods: Heart, brain and liver were harvested from rats before and after birth (D‐1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a low‐carbohydrate diet (D28F), and adults (D84). O ‐GlcNAc levels and regulatory enzymes were evaluated by western blots. Mass spectrometry (MS) approaches were performed to quantify levels of metabolites regulating O ‐GlcNAc and identify putative cardiac O ‐GlcNAcylated proteins. Results: Protein O ‐GlcNAc levels decrease drastically and progressively from D‐1 to D84 (13‐fold, P < .05) in the heart, whereas the changes were opposite in liver and brain. O ‐GlcNAc levels were unaffected by weaning diet in any tissues. Changes in expression of enzymes and levels of metabolites regulating O ‐GlcNAc were tissue‐dependent. MS analyses identified changes in putative cardiac O ‐GlcNAcylated proteins, namely those involved in the stress response and energy metabolism, such as ACAT1, which is only O ‐GlcNAcylated at D0. Conclusion: Our results demonstrate that protein O ‐GlcNAc levels are not linked to dietary intake and regulated in a time and tissue‐specific manner during postnatal development. We have identified by untargeted MS putative proteins with a particular O ‐GlcNAc signature across the development process suggesting specific role of these proteins.