Linked Life Data

14730207

Source:http://linkedlifedata.com/resource/pubmed/id/14730207

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-19
pubmed:abstractText
It is well documented that 17beta-estradiol (E(2)) exerts a cardiovascular protective effect. A possible role of E(2) in the regulation of endothelin-1 (ET-1) production has been reported. However, 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) 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 E(2), then stimulated with Ang II, and [(3)H]thymidine incorporation and ET-1 gene expression were examined. The effect of E(2) on Ang-II-induced extracellular signal-regulated kinase (ERK) phosphorylation was tested to elucidate the intracellular mechanism of E(2) in proliferation and ET-1 gene expression. Ang II increased DNA synthesis which was inhibited with E(2) (1- 100 nM). E(2), but not 17alpha-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 microM). E(2) 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, E(2) 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 E(2) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1021-7770
pubmed:author
pubmed:copyrightInfo
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-36
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14730207-Angiotensin II, pubmed-meshheading:14730207-Animals, pubmed-meshheading:14730207-Antioxidants, pubmed-meshheading:14730207-Aorta, pubmed-meshheading:14730207-Cell Division, pubmed-meshheading:14730207-Cells, Cultured, pubmed-meshheading:14730207-Down-Regulation, pubmed-meshheading:14730207-Endothelin-1, pubmed-meshheading:14730207-Estradiol, pubmed-meshheading:14730207-Female, pubmed-meshheading:14730207-Genes, Reporter, pubmed-meshheading:14730207-Humans, pubmed-meshheading:14730207-Male, pubmed-meshheading:14730207-Mitogen-Activated Protein Kinases, pubmed-meshheading:14730207-Muscle, Smooth, Vascular, pubmed-meshheading:14730207-Myocytes, Smooth Muscle, pubmed-meshheading:14730207-Rats, pubmed-meshheading:14730207-Rats, Sprague-Dawley, pubmed-meshheading:14730207-Reactive Oxygen Species, pubmed-meshheading:14730207-Signal Transduction
pubmed:articleTitle
17beta-estradiol downregulates angiotensin-II-induced endothelin-1 gene expression in rat aortic smooth muscle cells.
pubmed:affiliation
School of Chinese Medicine, China Medical University, Taichung, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't