Repository logo
  • Log In
    New user? Click here to register.Have you forgotten your password?
University College Dublin
  • Colleges & Schools
  • Statistics
  • All of DSpace
  • Log In
    New user? Click here to register.Have you forgotten your password?
  1. Home
  2. College of Science
  3. School of Biomolecular & Biomedical Science
  4. Biomolecular and Biomedical Science Research Collection
  5. Estrogen increases expression of the human prostacyclin receptor within the vasculature through an ERα-dependent mechanism
 
  • Details
Options

Estrogen increases expression of the human prostacyclin receptor within the vasculature through an ERα-dependent mechanism

File(s)
FileDescriptionSizeFormat
Download Turner E2 Reg of PrmIP JMB inc Supp Proofed.pdf747.2 KB
Alternative Title
Prostacyclin receptor gene regulation by estrogen
Author(s)
Turner, Elizebeth C. 
Kinsella, B. Therese 
Uri
http://hdl.handle.net/10197/3162
Date Issued
26 February 2010
Date Available
21T15:26:35Z September 2011
Abstract
Prostacyclin and the prostacyclin receptor (IP) are implicated in mediating many of the atheroprotective effects of estrogen in both humans and in animal models but through unknown mechanisms. Hence, herein the influence of estrogen on IP gene expression in endothelial EA.hy926, human erythroleukemia 92.1.7 and primary human (h) aortic smooth muscle (1o hAoSM) cells was investigated. Estrogen increased hIP mRNA levels, promoter (PrmIP)-directed reporter gene expression and cicaprost-dependent cAMP generation in all cell types, effects that were abrogated by actinomycinD and the general estrogen receptor (ER)-α/ERβ antagonist ICI 182,780. Furthermore, the ERα-selective agonist 4,4’,4ā€-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), but not the ERβ-agonist 2,3-bis(4-Hydroxyphenly)-propionitrile, significantly increased hIP mRNA and PrmIP-directed gene expression. Deletional and mutational analysis of PrmIP uncovered an evolutionary conserved estrogen-response element (ERE) while electrophoretic mobility shift, antibody-supershift and chromatin immunoprecipitations assays confirmed the direct binding of ERα, but not ERβ, to PrmIP both in vitro and in vivo. Moreover, immunofluorescence microscopy corroborated that estrogen and PPT increased hIP expression in 1o hAoSMCs. In conclusion, the hIP gene is directly regulated by estrogen that largely occurs through an ERα-dependent transcriptional mechanism and thereby provides critical insights into the role of prostacyclin/hIP in mediating the atheroprotective effects of estrogen within the human vasculature.
Sponsorship
Science Foundation Ireland
Health Research Board
Type of Material
Journal Article
Publisher
Elsevier
Journal
Journal of Molecular Biology
Volume
396
Issue
3
Start Page
473
End Page
486
Copyright (Published Version)
2010 Elsevier Ltd
Keywords
  • Prostacyclin receptor...

  • Estrogen

  • Gene expression

  • Transcription

  • Estrogen-response ele...

  • Promoter

Subject – LCSH
Prostacyclin--Receptors
Gene expression
Transcription factors
Estrogen
Promoters (Genetics)
DOI
10.1016/j.jmb.2010.01.010
Web versions
http://dx.doi.org/10.1016/j.jmb.2010.01.010
Language
English
Status of Item
Peer reviewed
ISSN
0022-2836
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-sa/1.0/
Owning collection
Biomolecular and Biomedical Science Research Collection
Scopus© citations
21
Acquisition Date
Jan 28, 2023
View Details
Views
1876
Last Month
20
Acquisition Date
Jan 28, 2023
View Details
Downloads
556
Last Week
3
Last Month
304
Acquisition Date
Jan 28, 2023
View Details
google-scholar
University College Dublin Research Repository UCD
The Library, University College Dublin, Belfield, Dublin 4
Phone: +353 (0)1 716 7583
Fax: +353 (0)1 283 7667
Email: mailto:research.repository@ucd.ie
Guide: http://libguides.ucd.ie/rru

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science

  • Cookie settings
  • Privacy policy
  • End User Agreement