17β-estradiol downregulates angiotensin-II-induced endothelin-1 gene expression in rat aortic smooth muscle cells

Hong Jye Hong, Ju Chi Liu, Paul Chan, Shu Hui Juan, Shih Hurng Loh, Jaung Geng Lin, Tzu-Hurng Cheng

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

It is well documented that 17β-estradiol (E2) exerts a cardiovascular protective effect. A possible role of E2 in the regulation of endothelin-1 (ET-1) production has been reported. However, the complex mechanisms by which E2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 may alter angiotensin II (Ang II)-induced cell proliferation and ET-1 gene expression and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with E2, then stimulated with Ang II, and [ 3H]thymidine incorporation and ET-1 gene expression were examined. The effect of E2 on Ang-II-induced extracellular signal-regulated kinase (ERK) phosphorylation was tested to elucidate the intracellular mechanism of E2 in proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was inhibited with E2 (1-100 nM). E2, but not 17α-estradiol, inhibited the Ang-II-induced ET-1 gene expression as revealed by Northern blotting and promoter activity assay. This effect was prevented by coincubation with the estrogen receptor antagonist ICI 182,780 (1 μM). E2 also inhibited Ang-II-increased intracellular reactive oxygen species (ROS) as measured by a redox-sensitive fluorescent dye, 2′,7′-dichlorofluorescin diacetate, and ERK phosphorylation. Furthermore, E2 and antioxidants, such as N-acetyl cysteine and diphenylene iodonium, decreased Ang-II-induced cell proliferation, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity. In summary, our results suggest that E2 inhibits Ang-II-induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway via attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalJournal of Biomedical Science
Volume11
Issue number1
DOIs
Publication statusPublished - 2004

Fingerprint

Endothelin-1
Gene expression
Angiotensin II
Smooth Muscle Myocytes
Muscle
Rats
Estradiol
Down-Regulation
Cells
Gene Expression
Extracellular Signal-Regulated MAP Kinases
Phosphorylation
Cell proliferation
Cell Proliferation
Reactive Oxygen Species
Acetylcysteine
Cardiovascular system
Transcription Factor AP-1
Cardiovascular System
Fluorescent Dyes

Keywords

  • 17β-Estradiol
  • Angiotensin II
  • Endothelin-1
  • Extracellular signal-regulated kinase
  • Reactive oxygen species
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

17β-estradiol downregulates angiotensin-II-induced endothelin-1 gene expression in rat aortic smooth muscle cells. / Hong, Hong Jye; Liu, Ju Chi; Chan, Paul; Juan, Shu Hui; Loh, Shih Hurng; Lin, Jaung Geng; Cheng, Tzu-Hurng.

In: Journal of Biomedical Science, Vol. 11, No. 1, 2004, p. 27-36.

Research output: Contribution to journalArticle

@article{ddc4a8eaa83941699456449ff5644c5a,
title = "17β-estradiol downregulates angiotensin-II-induced endothelin-1 gene expression in rat aortic smooth muscle cells",
abstract = "It is well documented that 17β-estradiol (E2) exerts a cardiovascular protective effect. A possible role of E2 in the regulation of endothelin-1 (ET-1) production has been reported. However, the complex mechanisms by which E2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 may alter angiotensin II (Ang II)-induced cell proliferation and ET-1 gene expression and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with E2, then stimulated with Ang II, and [ 3H]thymidine incorporation and ET-1 gene expression were examined. The effect of E2 on Ang-II-induced extracellular signal-regulated kinase (ERK) phosphorylation was tested to elucidate the intracellular mechanism of E2 in proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was inhibited with E2 (1-100 nM). E2, but not 17α-estradiol, inhibited the Ang-II-induced ET-1 gene expression as revealed by Northern blotting and promoter activity assay. This effect was prevented by coincubation with the estrogen receptor antagonist ICI 182,780 (1 μM). E2 also inhibited Ang-II-increased intracellular reactive oxygen species (ROS) as measured by a redox-sensitive fluorescent dye, 2′,7′-dichlorofluorescin diacetate, and ERK phosphorylation. Furthermore, E2 and antioxidants, such as N-acetyl cysteine and diphenylene iodonium, decreased Ang-II-induced cell proliferation, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity. In summary, our results suggest that E2 inhibits Ang-II-induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway via attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.",
keywords = "17β-Estradiol, Angiotensin II, Endothelin-1, Extracellular signal-regulated kinase, Reactive oxygen species, Smooth muscle cells",
author = "Hong, {Hong Jye} and Liu, {Ju Chi} and Paul Chan and Juan, {Shu Hui} and Loh, {Shih Hurng} and Lin, {Jaung Geng} and Tzu-Hurng Cheng",
year = "2004",
doi = "10.1159/000075286",
language = "English",
volume = "11",
pages = "27--36",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - 17β-estradiol downregulates angiotensin-II-induced endothelin-1 gene expression in rat aortic smooth muscle cells

AU - Hong, Hong Jye

AU - Liu, Ju Chi

AU - Chan, Paul

AU - Juan, Shu Hui

AU - Loh, Shih Hurng

AU - Lin, Jaung Geng

AU - Cheng, Tzu-Hurng

PY - 2004

Y1 - 2004

N2 - It is well documented that 17β-estradiol (E2) exerts a cardiovascular protective effect. A possible role of E2 in the regulation of endothelin-1 (ET-1) production has been reported. However, the complex mechanisms by which E2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 may alter angiotensin II (Ang II)-induced cell proliferation and ET-1 gene expression and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with E2, then stimulated with Ang II, and [ 3H]thymidine incorporation and ET-1 gene expression were examined. The effect of E2 on Ang-II-induced extracellular signal-regulated kinase (ERK) phosphorylation was tested to elucidate the intracellular mechanism of E2 in proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was inhibited with E2 (1-100 nM). E2, but not 17α-estradiol, inhibited the Ang-II-induced ET-1 gene expression as revealed by Northern blotting and promoter activity assay. This effect was prevented by coincubation with the estrogen receptor antagonist ICI 182,780 (1 μM). E2 also inhibited Ang-II-increased intracellular reactive oxygen species (ROS) as measured by a redox-sensitive fluorescent dye, 2′,7′-dichlorofluorescin diacetate, and ERK phosphorylation. Furthermore, E2 and antioxidants, such as N-acetyl cysteine and diphenylene iodonium, decreased Ang-II-induced cell proliferation, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity. In summary, our results suggest that E2 inhibits Ang-II-induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway via attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

AB - It is well documented that 17β-estradiol (E2) exerts a cardiovascular protective effect. A possible role of E2 in the regulation of endothelin-1 (ET-1) production has been reported. However, the complex mechanisms by which E2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 may alter angiotensin II (Ang II)-induced cell proliferation and ET-1 gene expression and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with E2, then stimulated with Ang II, and [ 3H]thymidine incorporation and ET-1 gene expression were examined. The effect of E2 on Ang-II-induced extracellular signal-regulated kinase (ERK) phosphorylation was tested to elucidate the intracellular mechanism of E2 in proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was inhibited with E2 (1-100 nM). E2, but not 17α-estradiol, inhibited the Ang-II-induced ET-1 gene expression as revealed by Northern blotting and promoter activity assay. This effect was prevented by coincubation with the estrogen receptor antagonist ICI 182,780 (1 μM). E2 also inhibited Ang-II-increased intracellular reactive oxygen species (ROS) as measured by a redox-sensitive fluorescent dye, 2′,7′-dichlorofluorescin diacetate, and ERK phosphorylation. Furthermore, E2 and antioxidants, such as N-acetyl cysteine and diphenylene iodonium, decreased Ang-II-induced cell proliferation, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1-mediated reporter activity. In summary, our results suggest that E2 inhibits Ang-II-induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway via attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

KW - 17β-Estradiol

KW - Angiotensin II

KW - Endothelin-1

KW - Extracellular signal-regulated kinase

KW - Reactive oxygen species

KW - Smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=0942278967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0942278967&partnerID=8YFLogxK

U2 - 10.1159/000075286

DO - 10.1159/000075286

M3 - Article

VL - 11

SP - 27

EP - 36

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

ER -