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Cited by 197Nitric Oxide and Endothelin EffectsPhytochemicals and Antioxidant ActivitiesPlant Gene Expression Analysis

Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment

Xu, Jin-Wen, Ikeda, Katsumi, Yamori, Yukio·2004·Hypertension
DOI 10.1161/01.hyp.0000135868.38343.c6
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Abstract

Endothelial nitric oxide synthase (eNOS) plays an important role in maintaining blood pressure homeostasis and vascular integrity. Natural dietary flavoniods are thought to protect against cardiovascular diseases by acting as antioxidants and vasodilatants. This study examined the effect of cyanidin-3-glucoside (Cy3G), a typical anthocyanin pigment, on eNOS expression. Treatment of bovine artery endothelial cells (BAECs) with Cy3G for 8 hours of enhanced eNOS protein expression in a dose- and time-dependent manner was determined by Western blot analysis. Longer incubation (12, 16, and 24 hours) of BAECs with 0.1 micromol/L of Cy3G caused a further increase in eNOS expression, and subsequently Cy3G also significantly increased nitric oxide output 2-fold (24 hours). Furthermore, Cy3G stimulated the phosphorylation of Src and extracellular signal-regulated kinase 1/2 (ERK1/2) in a time-dependent manner. An Src kinase inhibitor, pp2, and MEK inhibitor, PD98059, blocked the ERK1/2 phosphorylation and eNOS expression. Transfection with dominant-negative Src cDNA also inhibited the eNOS expression stimulated by Cy3G. In addition, stimulation with Cy3G for 30 minutes resulted in a phosphorylation of Sp1 that was blocked by PD98059. Cy3G enhanced the binding activity of the transcription factor Sp1 to the GC box in the proximal eNOS promoter of BAECs, as revealed by chromatin immunoprecipitation assay. The present study demonstrated that Cy3G induced eNOS expression and escalated NO production via an Src-ERK1/2-Sp1 signaling pathway in vascular endothelial cells. Increased eNOS expression may help to ameliorate endothelial dysfunction, harmonize blood pressure, and prevent atherosclerosis as long-term beneficial effects of flavoniods.

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  • Cyanidin-3-glucoside upregulates eNOS in bovine artery endothelial cells, and anthocyanin treatment (cyanidin and delphinidin) increases protein levels of eNOS in human umbilical vein endothelial cells.

    “Xu et al. and Lazze et al. have reported the upregulation of eNOS by cyanidin-3-glucoside in bovine artery endothelial cells, and increased protein levels of eNOS by anthocyanin treatment (cyanidin and delphinidin) in human umbilical vein endothelial cells.”

    From Berries: emerging impact on cardiovascular health (2010) · cites this paper as [68]

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Research works printed but not linked: 3

  1. Lorenz M, Wessler S, Follmann E, Michaelis W, Dusterhoft T, Baumann G, Stangl K, Stangl V. A constituent of green tea, epigallocatechin-3- gallate, activates endothelial nitric oxide synthase by a PI3K, PKA, and Akt-dependent pathway, and leads to endothelial-dependent vasore- laxation. J Biol Chem. 2004;279:6190 -6195.
  2. Rubin J, Murphy TC, Zhu L, Roy E, Nanes MS, Fan X. Mechanical strain differentially regulates eNOS and RANKL expression via ERK1/2 MAP kinase. J Biol Chem. 2003;278:34018 -34025.
  3. Nuedling S, Kahlert S, Loebbert K, Meyer R, Vetter H, Grohe C. Dif- ferential effects of 17␤-estradiol on mitogen-activated protein kinase pathway in rat cardiomyocytes. FEBS Lett. 1999;454:271-276.

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Authors
Xu, J.-W., Ikeda, K., & Yamori, Y.
Affiliations
Mukogawa Women's University (JP)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-08
Volume
44
Issue
2
Pages
217-222
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/01.hyp.0000135868.38343.c6
OpenAlex
W2100998391
Cited by
197
References
37
Citations by year
2026: 1 · 2025: 6 · 2024: 12 · 2023: 12 · 2022: 6 · 2021: 13 · 2020: 14 · 2019: 7 · 2018: 13 · 2017: 8 · 2016: 16 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 7
FWCI
4.32
Type
journal article
Language
en
Open access
closed
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant Gene Expression Analysis
Keywords
cyanidin-3-glucoside, anthocyanins, endothelial nitric oxide synthase, nitric oxide production, Src kinase, ERK1/2, Sp1, vascular endothelial cells, flavonoids, endothelial dysfunction, atherosclerosis, blood pressure
MeSH terms
Animals, Anthocyanins, Cattle, Cells, Cultured, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme Activation, Flavonoids, Glucosides, Phosphorylation, Pyrimidines, Up-Regulation, Sp1 Transcription Factor, Nitric Oxide Synthase, src-Family Kinases, Mitogen-Activated Protein Kinase 3, Nitric Oxide Synthase Type III

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