The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression

Huw S. Jones, Andrew Gordon, Simba G. Magwenzi, Khalid Naseem, Stephen Atkin, Fraser L. Courts

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Scope: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. Methods and results: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p<0.05) and increased superoxide production (136 ± 5 %, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47phox was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment. Conclusion: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47phox gene and protein expression. Quercetin restores key cellular signaling molecules (nitric oxide and superoxide) to normal levels in a model of vascular endothelial cell dysfunction.  This is achieved by restoring the levels of p47phox (a key component in the superoxide generating machinery NADPH oxidase) to normal levels.  The assessment of the modulation of these pathways by quercetin concentrations similar to those measured in human blood is a major part of the novelty of this work.

Original languageEnglish
Pages (from-to)787-797
Number of pages11
JournalMolecular Nutrition and Food Research
Volume60
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Fingerprint

angiotensin II
Quercetin
Human Umbilical Vein Endothelial Cells
flavonols
Angiotensin II
quercetin
Oxidation-Reduction
superoxide anion
Superoxides
nitric oxide
Nitric Oxide
NADPH Oxidase
protein kinase C
Protein Kinase C
Endothelial Cells
cell communication
antihypertensive effect
3-hydroxyflavone
human umbilical vein endothelial cells
cells

Keywords

  • Endothelial cells
  • NADPH oxidase
  • Nitric oxide
  • Quercetin
  • Superoxide

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression. / Jones, Huw S.; Gordon, Andrew; Magwenzi, Simba G.; Naseem, Khalid; Atkin, Stephen; Courts, Fraser L.

In: Molecular Nutrition and Food Research, Vol. 60, No. 4, 01.04.2016, p. 787-797.

Research output: Contribution to journalArticle

@article{8c111c3007ea4853a84cdcba294b9cde,
title = "The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression",
abstract = "Scope: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. Methods and results: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4{\%} p<0.05) and increased superoxide production (136 ± 5 {\%}, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47phox was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14{\%} of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51{\%}), however this was unaffected by quercetin co-treatment. Conclusion: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47phox gene and protein expression. Quercetin restores key cellular signaling molecules (nitric oxide and superoxide) to normal levels in a model of vascular endothelial cell dysfunction.  This is achieved by restoring the levels of p47phox (a key component in the superoxide generating machinery NADPH oxidase) to normal levels.  The assessment of the modulation of these pathways by quercetin concentrations similar to those measured in human blood is a major part of the novelty of this work.",
keywords = "Endothelial cells, NADPH oxidase, Nitric oxide, Quercetin, Superoxide",
author = "Jones, {Huw S.} and Andrew Gordon and Magwenzi, {Simba G.} and Khalid Naseem and Stephen Atkin and Courts, {Fraser L.}",
year = "2016",
month = "4",
day = "1",
doi = "10.1002/mnfr.201500751",
language = "English",
volume = "60",
pages = "787--797",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "4",

}

TY - JOUR

T1 - The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression

AU - Jones, Huw S.

AU - Gordon, Andrew

AU - Magwenzi, Simba G.

AU - Naseem, Khalid

AU - Atkin, Stephen

AU - Courts, Fraser L.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Scope: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. Methods and results: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p<0.05) and increased superoxide production (136 ± 5 %, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47phox was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment. Conclusion: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47phox gene and protein expression. Quercetin restores key cellular signaling molecules (nitric oxide and superoxide) to normal levels in a model of vascular endothelial cell dysfunction.  This is achieved by restoring the levels of p47phox (a key component in the superoxide generating machinery NADPH oxidase) to normal levels.  The assessment of the modulation of these pathways by quercetin concentrations similar to those measured in human blood is a major part of the novelty of this work.

AB - Scope: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. Methods and results: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p<0.05) and increased superoxide production (136 ± 5 %, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 μM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47phox was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment. Conclusion: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47phox gene and protein expression. Quercetin restores key cellular signaling molecules (nitric oxide and superoxide) to normal levels in a model of vascular endothelial cell dysfunction.  This is achieved by restoring the levels of p47phox (a key component in the superoxide generating machinery NADPH oxidase) to normal levels.  The assessment of the modulation of these pathways by quercetin concentrations similar to those measured in human blood is a major part of the novelty of this work.

KW - Endothelial cells

KW - NADPH oxidase

KW - Nitric oxide

KW - Quercetin

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=84959466080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959466080&partnerID=8YFLogxK

U2 - 10.1002/mnfr.201500751

DO - 10.1002/mnfr.201500751

M3 - Article

VL - 60

SP - 787

EP - 797

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 4

ER -