O-GlcNAc impairs endothelial function in uterine arteries from virgin but not pregnant rats: The role of GSK3β.

Autor: Dela Justina V; Graduate Program in Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil., Priviero F; Department of Physiology, Augusta University, Augusta, GA, USA., Dos Passos RR Jr; Graduate Program in Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil; Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, MT, Brazil., Webb RC; Department of Physiology, Augusta University, Augusta, GA, USA., Lima VV; Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, MT, Brazil., Giachini FR; Graduate Program in Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil; Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças, MT, Brazil. Electronic address: fernandagiachini@hotmail.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2020 Aug 05; Vol. 880, pp. 173133. Date of Electronic Publication: 2020 Apr 25.
DOI: 10.1016/j.ejphar.2020.173133
Abstrakt: Increased O-Linked β-N-acetylglucosamine (O-GlcNAc) is observed in several pathologies, and unbalanced O-GlcNAcylation levels favor endothelial dysfunction. Whether augmented O-GlcNAc impacts the uterine artery (UA) function and how it affects the UA during pregnancy remains to be elucidated. We hypothesized that glucosamine treatment increases O-GlcNAc, leading to uterine artery dysfunction and this effect is prevented by pregnancy. Pregnant (P) and non-pregnant (NP) Wistar rats were treated with glucosamine (300 mg/kg; i.p.) for 21 days. Concentration response-curves (CRC) to acetylcholine (in the presence or absence of L-NAME) and sodium nitroprusside were performed in UAs. In NP rats, glucosamine treatment increased O-GlcNAc expression in UAs accompanied by decreased endothelium-dependent relaxation, which was abolished by L-NAME. Endothelial nitric oxide synthase (eNOS) activity and total Akt expression were decreased by glucosamine-treatment in NP rats. Further, NP rats treated with glucosamine displayed increased glycogen synthase kinase 3 beta (GSK3β) activation and O-GlcNAc-transferase (OGT) expression in the UA. P rats treated with glucosamine displayed decreased O-GlcNAc in UAs and it was accompanied by improved relaxation to acetylcholine, whereas eNOS and GSK3β activity and total Akt and OGT expression were unchanged. Sodium nitroprusside-induced relaxation was not changed in all groups, indicating that glucosamine treatment led to endothelial dysfunction in NP rats. The underlying mechanism is, at least in part, dependent on Akt/GSK3β/OGT modulation. We speculate that during pregnancy, hormonal alterations play a protective role in preventing O-GlcNAcylation-induced endothelial dysfunction in the UAs.
Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest, financial or otherwise on this article.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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