Perinatal Protein Restriction Impacts Nuclear O-GalNAc Glycosylation in Cells of Liver and Brain Structures of the Rat

GARAY, YOHANA CAMILA; CEJAS, ROMINA BEATRIZ; PERONDI, MARIA CECILIA; GUTIÉRREZ, MARIA CECILIA; PARODI, PEDRO; FERRERO, FRANCO ALEJANDRO; LARDONE, RICARDO DANTE; VALDOMERO, ANALÍA; CUADRA, GABRIEL RICARDO; IRAZOQUI, FERNANDO JOSÉ

JOURNAL OF NUTRITION

AMER SOC NUTRITIONAL SCIENCE

Año: 2023

0022-3166

Background: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and an individual’s health. Objective: This study examined the influence of protein restriction during the perinatal period on the nuclear O-GalNAc glycosylation of cells from the liver and parts of the brain in the rat. Methods: Pregnant Wistar rats were divided into two groups on day 14 of pregnancy and fed ad libitum one of two isocaloric diets containing 24% (well-fed) or 8% (protein-restricted diet) casein until the end of experiment. Male pups were studied after weaning at 30 days of life. Animals and their organ/tissues (liver, cerebral cortex, cerebellum and hippocampus) were weighed. Cell nuclei were purified, and the presence in nucleus and cytoplasm of all factors required for the initiation of O-GalNAc glycan biosynthesis, i.e., the sugar donor (UDP-GalNAc), enzyme activity (ppGalNAc-transferase) and the glycosylation product (O-GalNAc glycans), were evaluated by western blotting, fluorescent microscopy, enzyme activity, enzyme-lectin sorbent assay and mass spectrometry. Results: The perinatal protein deficit reduced progeny weight, as well as cerebral cortex and cerebellum weight. UDP-GalNAc levels in the cytoplasm and nuclei of liver, cerebral cortex, cerebellum or hippocampus were not affected by the perinatal dietary protein deficits. However, this deficiency affected the ppGalNAc-transferase activity localized in the cerebral cortex and hippocampus cytoplasm as well as in the liver nucleus, thus reducing the “writing” ppGalNAc-transferase activity of O-GalNAc glycans. In addition, liver nucleoplasm from protein-restricted offspring revealed a significant reduction in the expression of O-GalNAc glycans on important nuclear proteins. Conclusions: Our results report an association between the consumption of a protein-restricted diet by the dam and her progeny with the modulation in the offsprings’ liver nuclei O-GalNAc glycosylation, which may ultimately regulate nuclear protein functions.