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)
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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 |
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Keywords: | Physiology (medical), physiology, pharmacology, general medicine. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Alves Moreira Lopes, Dr Rheure and Neves, Dr Karla |
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 > School of Cardiovascular & Metabolic Health |
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 |
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