J. Lipid Res. Acyl Labeled PIP's available August 1, 2008
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M500021-JLR200 on February 16, 2005

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M500021-JLR200v1
46/5/862    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smith, L. H.
Right arrow Articles by Vaughan, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, L. H.
Right arrow Articles by Vaughan, D. E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Lipid Research, Vol. 46, 862-871, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

The sterol response element binding protein regulates cyclooxygenase-2 gene expression in endothelial cells

Layton Harris Smith*, Matthew S. Petrie{dagger}, Jason D. Morrow§,**, John A. Oates§,** and Douglas E. Vaughan1,{dagger},§

* Departments of Pharmacology, Vanderbilt University Medical Center, Nashville, TN
§ Medicine, Vanderbilt University Medical Center, Nashville, TN
** Divisions of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN
{dagger} Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN

1 To whom correspondence should be addressed. e-mail: doug.vaughan{at}vanderbilt.edu

We previously demonstrated that cholesterol deprivation increases endothelial cyclooxygenase-2 (COX-2)-dependent prostacyclin [prostaglandin I2 (PGI2)] production in vitro. Cholesterol directly regulates gene transcription through the sterol response element binding protein (SREBP). In this work, we demonstrate that SREBP directly regulates COX-2 expression. Cholesterol reduces human COX-2 promoter-luciferase reporter construct activity in transiently transfected endothelial cells. Conversely, cotransfection with a constitutively active mutant SREBP increases COX-2 promoter activity. SREBP-1a and -2 specifically bind a putative sterol response element (SRE) sequence in the COX-2 promoter. This sequence competes for SREBP binding to a low density lipoprotein receptor consensus sequence in an electromobility-shift assay. These data indicate that endothelial COX-2 is regulated by cholesterol via the SREBP pathway.

The present study identifies COX-2 as the first vascular gene without a clear role in lipid metabolism transactivated by SREBP, and suggests that enhanced production of PGI2 through this pathway may be an additional benefit of cholesterol-lowering therapies.

Abbreviations: COX, cyclooxygenase; FBS, fetal bovine serum; HUVEC, human umbilical vein endothelial cell; LDL, low density lipoprotein; PGE2, prostaglandin E2; PGI2, prostaglandin I2; SREBP, sterol response element binding protein

Supplementary key words prostacyclin • cholesterol • HMG-CoA reductase inhibitor • lovastatin • vascular endothelial function


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.