SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

Huiming Zhang, Shikun He, Christine Spee, Keijiro Ishikawa, David R. Hinton

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

SIRT1, a NAD+ -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.

Original languageEnglish
Pages (from-to)549-552
Number of pages4
JournalCytokine
Volume76
Issue number2
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Choroidal Neovascularization
Vascular Endothelial Growth Factor A
Hypoxia-Inducible Factor 1
Phosphorylation
Histone Deacetylases
Retinal Pigments
Endothelial cells
Macular Degeneration
NAD
Assays
Endothelial Cells
Western Blotting
Epithelial Cells
Chemical activation
Enzyme-Linked Immunosorbent Assay
Therapeutics
resveratrol

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization. / Zhang, Huiming; He, Shikun; Spee, Christine; Ishikawa, Keijiro; Hinton, David R.

In: Cytokine, Vol. 76, No. 2, 01.12.2015, p. 549-552.

Research output: Contribution to journalArticle

Zhang, Huiming ; He, Shikun ; Spee, Christine ; Ishikawa, Keijiro ; Hinton, David R. / SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization. In: Cytokine. 2015 ; Vol. 76, No. 2. pp. 549-552.
@article{13f8047661c3441cbbba9a9c918562da,
title = "SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization",
abstract = "SIRT1, a NAD+ -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.",
author = "Huiming Zhang and Shikun He and Christine Spee and Keijiro Ishikawa and Hinton, {David R.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.cyto.2015.06.019",
language = "English",
volume = "76",
pages = "549--552",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

AU - Zhang, Huiming

AU - He, Shikun

AU - Spee, Christine

AU - Ishikawa, Keijiro

AU - Hinton, David R.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - SIRT1, a NAD+ -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.

AB - SIRT1, a NAD+ -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.

UR - http://www.scopus.com/inward/record.url?scp=84943816240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943816240&partnerID=8YFLogxK

U2 - 10.1016/j.cyto.2015.06.019

DO - 10.1016/j.cyto.2015.06.019

M3 - Article

VL - 76

SP - 549

EP - 552

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 2

ER -