HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M200386-JLR200v1 43/12/2172    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raspé, E. Articles by Staels, B. Search for Related Content PubMed PubMed Citation Articles by Raspé, E. Articles by Staels, B. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 43, 2172-2179, December 2002
Copyright © 2002 by Lipid Research, Inc.

Identification of Rev-erb as a physiological repressor of apoC-III gene transcription¹

Eric Raspé^2,*,, Hélène Duez^2,*, Anethe Mansén, Coralie Fontaine^*, Catherine Fiévet^*, Jean-Charles Fruchart^*,**, Bjorn Vennström and Bart Staels^3,*,**

^* UR 545 INSERM, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille, France
Groupe Merck, Centre de Recherche et Développement, 115 av. Lacassagne, 69003 Lyon, France
Karolinska Institute, Department of Cellular and Molecular Biology, S-17177 Stockholm, Sweden
^** Faculté de Pharmacie, Université de Lille II, 59006 Lille, France

³ To whom correspondence should be addressed. e-mail: bart.staels{at}pasteur-lille.fr

Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the present study, transient cotransfection experiments in rat hepatocytes in primary culture and rabbit kidney RK13 cells demonstrated that overexpression of Rev-erb specifically decreases basal and HNF-4 stimulated human apoC-III promoter activity. A Rev-erb response element was mapped by promoter deletion, mutation analysis, and gel-shift experiments to a AGGTCA half-site located at position -23/-18 (downstream of the TATA box) in the apoC-III promoter. Finally, Rev-erb-deficient mice displayed elevated serum and liver mRNA levels of apoC-III together with increased serum VLDL triglycerides.

Taken together, our data identify Rev-erb as a regulator of apoC-III gene expression, providing a novel, physiological role for this nuclear receptor in the regulation of lipid metabolism.

Supplementary key words apolipoprotein C-III • triglycerides • nuclear receptors

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

This article has been cited by other articles:

				V. T. Vasu, C. E. Cross, and K. Gohil Nr1d1, an Important Circadian Pathway Regulatory Gene, Is Suppressed By Cigarette Smoke in Murine Lungs Integr Cancer Ther, December 1, 2009; 8(4): 321 - 328. [Abstract] [PDF]

				M. Teboul, A. Grechez-Cassiau, F. Guillaumond, and F. Delaunay How nuclear receptors tell time J Appl Physiol, December 1, 2009; 107(6): 1965 - 1971. [Abstract] [Full Text] [PDF]

				H. Duez and B. Staels Rev-erb-{alpha}: an integrator of circadian rhythms and metabolism J Appl Physiol, December 1, 2009; 107(6): 1972 - 1980. [Abstract] [Full Text] [PDF]

				M. Teboul, F. Guillaumond, A. Grechez-Cassiau, and F. Delaunay Minireview: The Nuclear Hormone Receptor Family Round the Clock Mol. Endocrinol., December 1, 2008; 22(12): 2573 - 2582. [Abstract] [Full Text] [PDF]

				S. Hummasti and P. Tontonoz Adopting New Orphans into the Family of Metabolic Regulators Mol. Endocrinol., August 1, 2008; 22(8): 1743 - 1753. [Abstract] [Full Text] [PDF]

				C. Fontaine, E. Rigamonti, B. Pourcet, H. Duez, C. Duhem, J.-C. Fruchart, G. Chinetti-Gbaguidi, and B. Staels The Nuclear Receptor Rev-erb{alpha} Is a Liver X Receptor (LXR) Target Gene Driving a Negative Feedback Loop on Select LXR-Induced Pathways in Human Macrophages Mol. Endocrinol., August 1, 2008; 22(8): 1797 - 1811. [Abstract] [Full Text] [PDF]

				T. P. Burris Nuclear Hormone Receptors for Heme: REV-ERB{alpha} and REV-ERB{beta} Are Ligand-Regulated Components of the Mammalian Clock Mol. Endocrinol., July 1, 2008; 22(7): 1509 - 1520. [Abstract] [Full Text] [PDF]

				H. Duez and B. Staels The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 82 - 88. [Abstract] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]

				J. Wang, L. Yin, and M. A. Lazar The Orphan Nuclear Receptor Rev-erb{alpha} Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1 J. Biol. Chem., November 10, 2006; 281(45): 33842 - 33848. [Abstract] [Full Text] [PDF]

				S. N. Ramakrishnan, P. Lau, L. J. Burke, and G. E. O. Muscat Rev-erb{beta} Regulates the Expression of Genes Involved in Lipid Absorption in Skeletal Muscle Cells: EVIDENCE FOR CROSS-TALK BETWEEN ORPHAN NUCLEAR RECEPTORS AND MYOKINES J. Biol. Chem., March 11, 2005; 280(10): 8651 - 8659. [Abstract] [Full Text] [PDF]