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

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Souza-Silva, Leonardo and Alves-Lopes, Rheure and Silva Miguez, Jéssica and Dela Justina, Vanessa and Neves, Karla Bianca and Mestriner, Fabíola Leslie and Tostes, Rita de Cassia and Giachini, Fernanda Regina and Lima, Victor Vitorino (2018) Glycosylation with O-linked β-N-acetylglucosamine induces vascular dysfunction via production of superoxide anion/reactive oxygen species. Canadian Journal of Physiology and Pharmacology, 96 (3). pp. 232-240. ISSN 0008-4212 (https://doi.org/10.1139/cjpp-2017-0225)

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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 cells (VSMCs) were incubated with vehicle (methanol) or O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (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 reactive oxygen species, assessed by dihydroethidium fluorescence, and augmented •O2 − production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox-1 and Nox-4 protein expression in aortas and VSMCs. Translocation of the 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.

ORCID iDs

Souza-Silva, Leonardo, Alves-Lopes, Rheure, Silva Miguez, Jéssica, Dela Justina, Vanessa, Neves, Karla Bianca ORCID logoORCID: https://orcid.org/0000-0001-5158-9263, Mestriner, Fabíola Leslie, Tostes, Rita de Cassia, Giachini, Fernanda Regina and Lima, Victor Vitorino;
  • Item type:Article
    ID code:82958
    Dates:
    Date
    Event
    1 March 2018
    Published
    9 August 2017
    Published Online
    8 June 2017
    Accepted
    Notes:Funding Information: This work was supported in part by Fundação de Amparo à Pes-quisa do Estado de Mato Grosso (grant Nos. 151371/2014 (to F.R.G.) and 211917/2015 (to V.V.L.)), Coordenação de Aperfeiçoamento de Pes-soal de Nível Superior (grant No. 23038009165/2013-48 (to V.V.L.)), Fundação de Amparo à Pesquisa do Estado de São Paulo (grant Nos. 2008/58142-7 (to R.C.T.) and 2013/08216-2 (to the Center of Research on Inflammatory Diseases)), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant Nos. 445777/ 2014-1 (to V.V.L.) and 471675/2013/0 (to F.R.C.)). We would also like to thank the technical staff from our laboratories that contributed to the studies. Publisher Copyright: © 2018, Published by NRC Research Press.
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:27 Oct 2022 10:33
    Last modified:15 Dec 2024 01:38
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/82958
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