Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) induces vascular dysfunction via production of superoxide anion/reactive oxygen species

Souza-Silva, L., Alves-Lopes, R. , Silva Miguez, J., Dela Justina, V., Neves, K. B. , Mestriner, F. L., Tostes, R. C., Giachini, F. R. and Lima, V. V. (2018) Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) induces vascular dysfunction via production of superoxide anion/reactive oxygen species. Canadian Journal of Physiology and Pharmacology, 96(3), pp. 232-240. (doi:10.1139/cjpp-2017-0225) (PMID:28793197)

[img]
Preview
Text
145841.pdf - Accepted Version

941kB

Abstract

Overproduction of superoxide anion (•O2-) and O-linked β-N-acetylglucosamine (O-GlcNAc)-modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2- production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cell (VSMCs) were incubated with vehicle (methanol) or PUGNAc (100 µM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and Tiron, suggesting that •O2- contributes to endothelial dysfunction under augmented O-GlcNAc levels. Aortic segments incubated with PUGNAc also exhibited increased levels of ROS, assessed by dihydroethidium fluorescence, and augmented •O2- production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox1 and Nox4 protein expression in aorta and VSMCs. Translocation of p47phox subunit from the cytosol to the membrane was greater in aortas incubated with PUGNAc. VSMCs displayed increased p22phox protein expression after PUGNAc incubation, suggesting that NADPH oxidase is activated in conditions where O-GlcNAc protein levels are increased. In conclusion, O-GlcNAc levels reduce endothelium-dependent relaxation by overproduction of •O2- via activation of NADPH oxidase. This may represent an additional mechanism by which augmented O-GlcNAc levels impair vascular function.

Item Type:Articles
Keywords:Physiology (medical), physiology, pharmacology, general medicine.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lopes, Dr Rheure and Neves, Dr Karla Bianca
Authors: Souza-Silva, L., Alves-Lopes, R., Silva Miguez, J., Dela Justina, V., Neves, K. B., Mestriner, F. L., Tostes, R. C., Giachini, F. R., and Lima, V. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Canadian Journal of Physiology and Pharmacology
Publisher:Canadian Science Publishing
ISSN:0008-4212
ISSN (Online):1205-7541
Published Online:09 August 2017
Copyright Holders:Copyright © 2017 Canadian Science Publishing
First Published:First published in Canadian Journal of Physiology and Pharmacology 96(3):232-240
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record