Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells

Shu Hui Juan, Tzu-Hurng Cheng, Hui Chen Lin, Yen Ling Chu, Wen Sen Lee

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Resveratrol-mediated heme oxygenase-1 (HO-1) induction has been shown to occur in primary neuronal cultures and is thought to have potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine resveratrol's HO-1 inducing potency and its induction regulation in human aortic smooth muscle cells (HASMC). We showed that resveratrol-mediated HO-1 induction occurred in concentration- and time-dependent manners, but only at low concentrations (1-10 μM), and that it was modulated at both the transcription and translation levels. Additionally, the results of our study showed that nuclear factor-kappa B (NF-κB) inhibitors eliminated resveratrol-mediated HO-1 induction and promoter activity, and that deletion of NF-κB binding sites in the HO-1 promoter region strongly reduced promoter activity, suggesting involvement of the NF-κB pathway in HO-1 induction by resveratrol. Suppression of NF-κB activity by resveratrol at high concentrations (≥20 μM) has been reported to be attributed to its anti-inflammatory and anti-oxidative properties. Likewise, we showed that resveratrol at concentrations of ≥20 μM blocked the activity of NF-κB through suppression of I kappa-B alpha (IκBα) phosphorylation, which caused inhibition of HO-1 induction. Conversely, resveratrol in a range of 1-10 μM enhanced the phosphorylation and degradation of IκBα, a key step in NF-κB activation, resulting in HO-1 induction. Collectively, we suggest that resveratrol-mediated HO-1 expression occurs, at least in part, through the NF-κB pathway, which might contribute to resveratrol's vascular-protective effect at physiological concentrations after moderate red wine consumption.

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalBiochemical Pharmacology
Volume69
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Fingerprint

Heme Oxygenase-1
Smooth Muscle Myocytes
Muscle
Cells
NF-kappa B
Phosphorylation
I-kappa B Proteins
resveratrol
Wine
Transcription
Genetic Promoter Regions
Action Potentials
Coronary Disease
Blood Vessels
Anti-Inflammatory Agents
Antioxidants
Chemical activation
Binding Sites

Keywords

  • c-Jun N-terminal kinase
  • Extracellular signal-regulated kinase 1/2
  • Heme oxygenase-1
  • Human aortic smooth muscle cell
  • I kappa-B alpha
  • Mitogen-activated protein kinases
  • Nuclear factor-κB
  • Resveratrol

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. / Juan, Shu Hui; Cheng, Tzu-Hurng; Lin, Hui Chen; Chu, Yen Ling; Lee, Wen Sen.

In: Biochemical Pharmacology, Vol. 69, No. 1, 01.01.2005, p. 41-48.

Research output: Contribution to journalArticle

@article{d14b2a6c9bd2466bbfd0ada80d5615b1,
title = "Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells",
abstract = "Resveratrol-mediated heme oxygenase-1 (HO-1) induction has been shown to occur in primary neuronal cultures and is thought to have potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine resveratrol's HO-1 inducing potency and its induction regulation in human aortic smooth muscle cells (HASMC). We showed that resveratrol-mediated HO-1 induction occurred in concentration- and time-dependent manners, but only at low concentrations (1-10 μM), and that it was modulated at both the transcription and translation levels. Additionally, the results of our study showed that nuclear factor-kappa B (NF-κB) inhibitors eliminated resveratrol-mediated HO-1 induction and promoter activity, and that deletion of NF-κB binding sites in the HO-1 promoter region strongly reduced promoter activity, suggesting involvement of the NF-κB pathway in HO-1 induction by resveratrol. Suppression of NF-κB activity by resveratrol at high concentrations (≥20 μM) has been reported to be attributed to its anti-inflammatory and anti-oxidative properties. Likewise, we showed that resveratrol at concentrations of ≥20 μM blocked the activity of NF-κB through suppression of I kappa-B alpha (IκBα) phosphorylation, which caused inhibition of HO-1 induction. Conversely, resveratrol in a range of 1-10 μM enhanced the phosphorylation and degradation of IκBα, a key step in NF-κB activation, resulting in HO-1 induction. Collectively, we suggest that resveratrol-mediated HO-1 expression occurs, at least in part, through the NF-κB pathway, which might contribute to resveratrol's vascular-protective effect at physiological concentrations after moderate red wine consumption.",
keywords = "c-Jun N-terminal kinase, Extracellular signal-regulated kinase 1/2, Heme oxygenase-1, Human aortic smooth muscle cell, I kappa-B alpha, Mitogen-activated protein kinases, Nuclear factor-κB, Resveratrol",
author = "Juan, {Shu Hui} and Tzu-Hurng Cheng and Lin, {Hui Chen} and Chu, {Yen Ling} and Lee, {Wen Sen}",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.bcp.2004.09.015",
language = "English",
volume = "69",
pages = "41--48",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells

AU - Juan, Shu Hui

AU - Cheng, Tzu-Hurng

AU - Lin, Hui Chen

AU - Chu, Yen Ling

AU - Lee, Wen Sen

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Resveratrol-mediated heme oxygenase-1 (HO-1) induction has been shown to occur in primary neuronal cultures and is thought to have potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine resveratrol's HO-1 inducing potency and its induction regulation in human aortic smooth muscle cells (HASMC). We showed that resveratrol-mediated HO-1 induction occurred in concentration- and time-dependent manners, but only at low concentrations (1-10 μM), and that it was modulated at both the transcription and translation levels. Additionally, the results of our study showed that nuclear factor-kappa B (NF-κB) inhibitors eliminated resveratrol-mediated HO-1 induction and promoter activity, and that deletion of NF-κB binding sites in the HO-1 promoter region strongly reduced promoter activity, suggesting involvement of the NF-κB pathway in HO-1 induction by resveratrol. Suppression of NF-κB activity by resveratrol at high concentrations (≥20 μM) has been reported to be attributed to its anti-inflammatory and anti-oxidative properties. Likewise, we showed that resveratrol at concentrations of ≥20 μM blocked the activity of NF-κB through suppression of I kappa-B alpha (IκBα) phosphorylation, which caused inhibition of HO-1 induction. Conversely, resveratrol in a range of 1-10 μM enhanced the phosphorylation and degradation of IκBα, a key step in NF-κB activation, resulting in HO-1 induction. Collectively, we suggest that resveratrol-mediated HO-1 expression occurs, at least in part, through the NF-κB pathway, which might contribute to resveratrol's vascular-protective effect at physiological concentrations after moderate red wine consumption.

AB - Resveratrol-mediated heme oxygenase-1 (HO-1) induction has been shown to occur in primary neuronal cultures and is thought to have potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine resveratrol's HO-1 inducing potency and its induction regulation in human aortic smooth muscle cells (HASMC). We showed that resveratrol-mediated HO-1 induction occurred in concentration- and time-dependent manners, but only at low concentrations (1-10 μM), and that it was modulated at both the transcription and translation levels. Additionally, the results of our study showed that nuclear factor-kappa B (NF-κB) inhibitors eliminated resveratrol-mediated HO-1 induction and promoter activity, and that deletion of NF-κB binding sites in the HO-1 promoter region strongly reduced promoter activity, suggesting involvement of the NF-κB pathway in HO-1 induction by resveratrol. Suppression of NF-κB activity by resveratrol at high concentrations (≥20 μM) has been reported to be attributed to its anti-inflammatory and anti-oxidative properties. Likewise, we showed that resveratrol at concentrations of ≥20 μM blocked the activity of NF-κB through suppression of I kappa-B alpha (IκBα) phosphorylation, which caused inhibition of HO-1 induction. Conversely, resveratrol in a range of 1-10 μM enhanced the phosphorylation and degradation of IκBα, a key step in NF-κB activation, resulting in HO-1 induction. Collectively, we suggest that resveratrol-mediated HO-1 expression occurs, at least in part, through the NF-κB pathway, which might contribute to resveratrol's vascular-protective effect at physiological concentrations after moderate red wine consumption.

KW - c-Jun N-terminal kinase

KW - Extracellular signal-regulated kinase 1/2

KW - Heme oxygenase-1

KW - Human aortic smooth muscle cell

KW - I kappa-B alpha

KW - Mitogen-activated protein kinases

KW - Nuclear factor-κB

KW - Resveratrol

UR - http://www.scopus.com/inward/record.url?scp=9944248650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9944248650&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2004.09.015

DO - 10.1016/j.bcp.2004.09.015

M3 - Article

C2 - 15588712

AN - SCOPUS:9944248650

VL - 69

SP - 41

EP - 48

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 1

ER -