Abstract

It has been well documented previously that 17β-estradiol (E 2) exerts a protective effect on cardiovascular tissue. The possible role of E 2 in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E 2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E 2 (1-100 nM), but not 17α-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E 2 was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 μM). E 2 also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2′,7′-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E 2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E 2 inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers 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)H1254-H1261
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number3 56-3
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Endothelin-1
Estradiol
Endothelial Cells
Gene Expression
Extracellular Signal-Regulated MAP Kinases
Reactive Oxygen Species
Phosphorylation
NADPH Oxidase
Transcription Factor AP-1
Acetylcysteine
Cardiovascular System
Fluorescent Dyes
Protein Binding
Oxidation-Reduction
Cultured Cells
Estrogens
Antioxidants
Messenger RNA
Peptides

Keywords

  • Extracellular signal-regulated kinase
  • Reactive oxygen species
  • Strain

ASJC Scopus subject areas

  • Physiology

Cite this

17β-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells. / Juan, Shu Hui; Chen, Jin Jer; Chen, Cheng Hsien; Lin, Heng; Cheng, Ching Feng; Liu, Ju Chi; Hsieh, Ming Hsiung; Chen, Yen Ling; Chao, Hung Hsing; Chen, Tso Hsiao; Chan, Paul; Cheng, Tzu-Hurng.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287, No. 3 56-3, 09.2004, p. H1254-H1261.

Research output: Contribution to journalArticle

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title = "17β-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells",
abstract = "It has been well documented previously that 17β-estradiol (E 2) exerts a protective effect on cardiovascular tissue. The possible role of E 2 in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E 2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E 2 (1-100 nM), but not 17α-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E 2 was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 μM). E 2 also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2′,7′-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E 2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E 2 inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.",
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author = "Juan, {Shu Hui} and Chen, {Jin Jer} and Chen, {Cheng Hsien} and Heng Lin and Cheng, {Ching Feng} and Liu, {Ju Chi} and Hsieh, {Ming Hsiung} and Chen, {Yen Ling} and Chao, {Hung Hsing} and Chen, {Tso Hsiao} and Paul Chan and Tzu-Hurng Cheng",
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T1 - 17β-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells

AU - Juan, Shu Hui

AU - Chen, Jin Jer

AU - Chen, Cheng Hsien

AU - Lin, Heng

AU - Cheng, Ching Feng

AU - Liu, Ju Chi

AU - Hsieh, Ming Hsiung

AU - Chen, Yen Ling

AU - Chao, Hung Hsing

AU - Chen, Tso Hsiao

AU - Chan, Paul

AU - Cheng, Tzu-Hurng

PY - 2004/9

Y1 - 2004/9

N2 - It has been well documented previously that 17β-estradiol (E 2) exerts a protective effect on cardiovascular tissue. The possible role of E 2 in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E 2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E 2 (1-100 nM), but not 17α-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E 2 was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 μM). E 2 also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2′,7′-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E 2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E 2 inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

AB - It has been well documented previously that 17β-estradiol (E 2) exerts a protective effect on cardiovascular tissue. The possible role of E 2 in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E 2 inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E 2 was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E 2 (1-100 nM), but not 17α-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E 2 was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 μM). E 2 also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2′,7′-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E 2 and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E 2 inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

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