The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression

Urizar, Nancy L., Dowhan, Dennis H. and Moore, David D. (2000) The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. The Journal of Biological Chemistry, 275 50: 39313-39317. doi:10.1074/jbc.M007998200

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Author Urizar, Nancy L.
Dowhan, Dennis H.
Moore, David D.
Title The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2000-12-15
Sub-type Article (original research)
DOI 10.1074/jbc.M007998200
Open Access Status File (Publisher version)
Volume 275
Issue 50
Start page 39313
End page 39317
Total pages 5
Place of publication Bethesda, MD, USA
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 060199 Biochemistry and Cell Biology not elsewhere classified
Formatted abstract
Bile acids facilitate the absorption of dietary lipids and fat-soluble vitamins and are physiological ligands for the farnesoid X-activated receptor (FXR), a member of the nuclear hormone receptor superfamily. FXR functions as a heterodimer with the retinoid X receptor and in the presence of ligand, the heterodimer binds to specific DNA sequences in the promoters of target genes to regulate gene transcription. Phospholipid transfer protein (PLTP) has been identified as a possible target gene for FXR because the human promoter contains a potential FXR response element, an inverted repeat in which consensus receptor-binding hexamers are separated by one nucleotide (inverted repeat-1). PLTP is essential in the transfer of very low density lipoprotein phospholipids into high density lipoprotein (Jiang, X. C., Bruce, C., Mar, J., Lin, M., Ji, Y., Francone, O. L., and Tall, A. R. (1999) J. Clin. Invest. 103, 907–914). Here we report the regulation of PLTP gene expression by FXR and bile acids. In CV-1 cells, cotransfection of FXR and the retinoid X receptor resulted in bile acid-dependent transactivation of a luciferase reporter construct containing the human PLTP promoter. Mutation analysis demonstrated that the inverted repeat-1 (IR-1) in the PLTP promoter is required for this transactivation. Finally, we demonstrate that bile acids are able to regulate PLTP gene expression in vivo. Mice fed a chow diet supplemented with bile acid showed increased hepatic PLTP mRNA levels. These results suggest that FXR may play a role in high density lipoprotein metabolism via the regulation of PLTP gene expression.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Tue, 20 Jul 2010, 20:05:03 EST by Laura McTaggart on behalf of UQ Diamantina Institute