O-GlcNAc impairs endothelial function in uterine arteries from virgin but not pregnant rats: The role of GSK3β
| Autor: | Victor V. Lima, Rinaldo Rodrigues dos Passos, Vanessa Dela Justina, Fernanda Priviero, R. Clinton Webb, Fernanda R. Giachini |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nitric Oxide Synthase Type III N-Acetylglucosaminyltransferases Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos Glucosamine Pregnancy Internal medicine medicine.artery medicine Animals Endothelial dysfunction Rats Wistar Uterine artery Protein kinase B Pharmacology Glycogen Synthase Kinase 3 beta biology Chemistry Kinase medicine.disease biology.organism_classification Vasodilation Uterine Artery 030104 developmental biology Endocrinology Female Sodium nitroprusside Endothelium Vascular Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Acetylcholine medicine.drug |
| Zdroj: | Eur J Pharmacol |
| ISSN: | 1879-0712 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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