Perinatal Protein Deprivation Impacts Nuclear O-GalNAc Glycosylation in Rat Pup Cells

GARAY, YC; CEJAS, RB; PERONDI, MC; GUTIERREZ, MC; PARODI, P; FERRERO, FA; LARDONE RD; VALDOMERO A; CUADRA GR; IRAZOQUI FJ

Congreso; SAIB; 2021

Background: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and individual health. Objective: Here we studied the influence of early undernutrition on the nuclear O-GalNAc glycosylation of rat pup cells. Methods: Pregnant rats were fed with well-nourished or protein-deprived diets, and after weaning at 30 days, pups were studied. Results: Perinatal protein deficit exerted a direct consequence on offspring development, reducing the progeny weight. In different offspring tissues, we analyzed for the presence in nucleus of all the factors involved in the beginning of O-GalNAc glycan biosynthesis: the substrate donor (UDP-GalNAc), the enzyme activity (ppGalNAc-T) and the glycosylation product (O-GalNAc glycans). UDP-GalNAc levels in cytoplasm and nucleus were not affected by perinatal protein deficit in liver, cerebral cortex, cerebellum and hippocampus. However, perinatal protein deficiency affected the total activity of ppGalNAc-T localized in liver nucleus, thus reducing the ?writing? ppGalNAc-T activity of nuclear O-GalNAc glycans. In addition, liver nucleoplasms from protein-deprived pups reported a reduction in the expression of nuclear O-GalNAc glycans. Conclusions: Our results suggest that limited availability of essential amino acids during early life stages (gestation and lactation) can modulate nuclear O-GalNAc glycosylation, which might ultimately regulate nuclear protein functions.