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Publication : Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes.

First Author  Damiano F Year  2012
Journal  Int J Biochem Cell Biol Volume  44
Issue  4 Pages  659-68
PubMed ID  22249025 Mgi Jnum  J:320384
Mgi Id  MGI:6861916 Doi  10.1016/j.biocel.2012.01.003
Citation  Damiano F, et al. (2012) Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes. Int J Biochem Cell Biol 44(4):659-68
abstractText  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 PPARalpha, and in murine 3T3-L1 adipocytes treated with rosiglitazone, agonist of PPARgamma. The overexpression of PPARalpha/RXRalpha and PPARgamma/RXRalpha 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 PPARalpha and PPARgammain vivo was confirmed by ChIP assay in BRL-3A and 3T3-L1 cells, respectively.
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