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

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 s...

Full description

Bibliographic Details
Main Authors:	Lau, Y.S., Mustafa, M.R., Choy, K.W., Chan, S.M.H., Potocnik, S., Herbert, T.P., Woodman, O.L.
Format:	Article
Published:	Nature Publishing Group 2018
Subjects:	Q Science (General) R Medicine
Online Access:	http://dx.doi.org/10.1038/s41598-018-19584-8 http://dx.doi.org/10.1038/s41598-018-19584-8 http://eprints.um.edu.my/18976/1/3%E2%80%B2%2C4%E2%80%B2%2Ddihydroxyflavonol_ameliorates_endoplasmic_reticulum_stress%2Dinduced_apoptosis_and_endothelial_dysfunction_in_mice.pdf

id	um-18976
recordtype	eprints
spelling	um-189762018-08-07T07:49:41Z 3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice Lau, Y.S. Mustafa, M.R. Choy, K.W. Chan, S.M.H. Potocnik, S. Herbert, T.P. Woodman, O.L. Q Science (General) R Medicine 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. Nature Publishing Group 2018 Article PeerReviewed application/pdf http://eprints.um.edu.my/18976/1/3%E2%80%B2%2C4%E2%80%B2%2Ddihydroxyflavonol_ameliorates_endoplasmic_reticulum_stress%2Dinduced_apoptosis_and_endothelial_dysfunction_in_mice.pdf http://dx.doi.org/10.1038/s41598-018-19584-8 Lau, Y.S.; Mustafa, M.R.; Choy, K.W.; Chan, S.M.H.; Potocnik, S.; Herbert, T.P.; Woodman, O.L. (2018) 3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice. Scientific Reports <http://eprints.um.edu.my/view/publication/Scientific_Reports.html>, 8 (1). pp. 1-10. ISSN 2045-2322 http://eprints.um.edu.my/18976/
repository_type	Digital Repository
institution_category	Local University
institution	University Malaya
building	UM Research Repository
collection	Online Access
topic	Q Science (General) R Medicine
spellingShingle	Q Science (General) R Medicine Lau, Y.S. Mustafa, M.R. Choy, K.W. Chan, S.M.H. Potocnik, S. Herbert, T.P. Woodman, O.L. 3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
description	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.
format	Article
author	Lau, Y.S. Mustafa, M.R. Choy, K.W. Chan, S.M.H. Potocnik, S. Herbert, T.P. Woodman, O.L.
author_facet	Lau, Y.S. Mustafa, M.R. Choy, K.W. Chan, S.M.H. Potocnik, S. Herbert, T.P. Woodman, O.L.
author_sort	Lau, Y.S.
title	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
title_short	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
title_full	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
title_fullStr	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
title_full_unstemmed	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
title_sort	3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
publisher	Nature Publishing Group
publishDate	2018
url	http://dx.doi.org/10.1038/s41598-018-19584-8 http://dx.doi.org/10.1038/s41598-018-19584-8 http://eprints.um.edu.my/18976/1/3%E2%80%B2%2C4%E2%80%B2%2Ddihydroxyflavonol_ameliorates_endoplasmic_reticulum_stress%2Dinduced_apoptosis_and_endothelial_dysfunction_in_mice.pdf
first_indexed	2018-09-06T06:55:19Z
last_indexed	2018-09-06T06:55:19Z
_version_	1610840193284177920

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

Similar Items