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Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2012 Apr; Vol. 44 (4), pp. 659-68. Date of Electronic Publication: 2012 Jan 10. - Publication Year :
- 2012
-
Abstract
- Citrate carrier (CiC), a mitochondrial inner membrane protein, is an essential component of the shuttle system which transports acetyl-CoA from mitochondria to the cytosol where lipogenesis occurs. CiC is regulated by SREBP-1, a transcription factor that controls the expression of several lipogenic genes. CiC is also implicated in cholesterol synthesis, glycolysis and gluconeogenesis, suggesting that besides SREBP-1 other transcription factors could modulate the expression of its gene. Here, we provide evidences demonstrating that CiC expression is regulated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma in hepatocytes and adipocytes, respectively. CiC expression increased in rat BRL-3A hepatocytes treated with WY-14,643, agonist of PPARα, and in murine 3T3-L1 adipocytes treated with rosiglitazone, agonist of PPARγ. The overexpression of PPARα/RXRα and PPARγ/RXRα heterodimer enhanced CiC promoter activity in BRL-3A and 3T3-L1, respectively. Luciferase reporter gene and gel mobility shift assays indicated that a functional peroxisome proliferator-activated receptor response element (PPRE), identified in the CiC promoter, conferred responsiveness to activation by PPARs. The binding of PPRE of CiC promoter by PPARα and PPARγin vivo was confirmed by ChIP assay in BRL-3A and 3T3-L1 cells, respectively.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adipocytes cytology
Adipocytes drug effects
Animals
Base Sequence
Cell Differentiation drug effects
Docosahexaenoic Acids pharmacology
Genes, Reporter genetics
Hepatocytes cytology
Hepatocytes drug effects
Humans
Luciferases genetics
Mice
Promoter Regions, Genetic drug effects
Protein Binding
Rats
Response Elements drug effects
Response Elements genetics
Transcriptional Activation drug effects
Adipocytes metabolism
Carrier Proteins genetics
Hepatocytes metabolism
PPAR alpha metabolism
PPAR gamma metabolism
Promoter Regions, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 44
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 22249025
- Full Text :
- https://doi.org/10.1016/j.biocel.2012.01.003