학술논문

Perinatal Protein Restriction Impacts Nuclear O-GalNAc Glycosylation in Cells of Liver and Brain Structures of the Rat.
Document Type
Academic Journal
Author
Garay YC; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Cejas RB; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Perondi MC; Instituto de Farmacología Experimental de Córdoba, IFEC, CONICET, and Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Gutiérrez MC; Instituto de Farmacología Experimental de Córdoba, IFEC, CONICET, and Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Parodi P; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Ferrero FA; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Lardone RD; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Valdomero A; Instituto de Farmacología Experimental de Córdoba, IFEC, CONICET, and Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Cuadra GR; Instituto de Farmacología Experimental de Córdoba, IFEC, CONICET, and Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina.; Irazoqui FJ; Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC, CONICET, and Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, the Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, the Córdoba, Argentina. Electronic address: fernando.irazoqui@unc.edu.ar.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 0404243 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1541-6100 (Electronic) Linking ISSN: 00223166 NLM ISO Abbreviation: J Nutr Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and an individual's health.
Objectives: This study examined the influence of protein restriction during the perinatal period on the nuclear O-N-acetylgalactosamine (O-GalNAc) glycosylation of cells from the liver and parts of the brain in the rat.
Methods: Pregnant Wistar rats were divided into 2 groups on day 14 of pregnancy and fed ad libitum 1 of 2 isocaloric diets containing 24% (well-fed) or 8% (protein-restricted diet) casein until the end of the experiment. Male pups were studied after weaning at 30 d 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 the cerebral cortex and cerebellum weight. UDP-GalNAc levels in the cytoplasm and nuclei of the liver, the 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 offspring' liver nuclei O-GalNAc glycosylation, which may ultimately regulate nuclear protein functions.
(Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)