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

Lau, Y.S. and Mustafa, Mohd Rais and Choy, K.W. and Chan, S.M.H. and Potocnik, S. and Herbert, T.P. and Woodman, O.L. (2018) 3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice. Scientific Reports, 8 (1). pp. 1-10. ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-018-19584-8.

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Official URL: http://dx.doi.org/10.1038/s41598-018-19584-8


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.

Item Type: Article
Funders: Ministry of Higher Education (MoHE High Impact Research Grant H-20001- 00-E000055), Australian Endeavour Fellowship (number: 4382-2015)
Uncontrolled Keywords: 3′,4′-dihydroxyflavonol; Ameliorates ; Endoplasmic reticulum; Stress-induced apoptosis; Endothelial dysfunction; Mice
Subjects: Q Science > Q Science (General)
R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 07 Aug 2018 07:49
Last Modified: 16 Dec 2019 09:25
URI: http://eprints.um.edu.my/id/eprint/18976

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