3 ',4 '-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice

Lau, Y, Mustafa, M, Choy, K, Chan, S, Potocnik, S, Herbert, T and Woodman, O 2018, '3 ',4 '-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice', Scientific Reports, vol. 8, no. 1, pp. 1-10.


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Collection: Journal Articles

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Title 3 ',4 '-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
Author(s) Lau, Y
Mustafa, M
Choy, K
Chan, S
Potocnik, S
Herbert, T
Woodman, O
Year 2018
Journal name Scientific Reports
Volume number 8
Issue number 1
Start page 1
End page 10
Total pages 10
Publisher Nature
Abstract Endoplasmic reticulum (ER) stress has been implicated in the development of hypertension 3 through the induction of endothelial impairment. As 3′,4′-dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to attenuate ER stress, we investigated whether DiOHF can protect mice from ER stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with tunicamycin to induce ER stress in the presence or absence of either DiOHF or tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin elevated blood pressure and impaired endothelium-dependent relaxation. Moreover, in aortae there was evidence of ER stress, oxidative stress and reduced NO production. This was coincident with increased NOX2 expression and reduced phosphorylation of endothelial nitric oxide synthase (eNOS) on Ser1176. Importantly, the effects of tunicamycin were significantly ameliorated by DiOHF or TUDCA. DiOHF also inhibited tunicamycin-induced ER stress and apoptosis in cultured human endothelial cells (HUVEC). These results provide evidence that ER stress is likely an important initiator of endothelial dysfunction through the induction of oxidative stress and a reduction in NO synthesis and that DiOHF directly protects against ER stress- induced injury. DiOHF may be useful to prevent ER and oxidative stress to preserve endothelial function, for example in hypertension.
Subject Signal Transduction
Pharmaceutical Sciences
Systems Physiology
Cell Physiology
Keyword(s) Unfolded Protein Response
Programmed Cell-Death
ER Stress
Cardiac Damage
Hypertension
Rat
Atherosclerosis
Homocysteine
Reperfusion
Inhibition
DOI - identifier 10.1038/s41598-018-19584-8
Copyright notice © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. To view a copy of this license, visit: http://creativecommons.org/licenses/by/4.0/.
ISSN 2045-2322
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