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Bile Acids Induce Diacyglycerol Kinase‐θ Expression in HepG2 liver Cells
Author(s) -
Cai Kai,
Sewer Marion B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.790.11
Subject(s) - diacylglycerol kinase , farnesoid x receptor , nuclear receptor , phosphatidic acid , liver x receptor , g protein coupled bile acid receptor , chenodeoxycholic acid , bile acid , reporter gene , intracellular , biology , kinase , signal transduction , microbiology and biotechnology , gene expression , chemistry , biochemistry , protein kinase c , gene , transcription factor , phospholipid , membrane
Diacylglycerol kinases (DGKs) are intracellular lipid kinases that catalyze the conversion of diacylglycerol into phosphatidic acid (PA), thus regulating the intracellular concentrations of these two bioactive signaling lipids. We have found that DGK‐θ, the sole member of the type V family of DGK isoforms, is expressed in the nucleus of HepG2 cells. To determine the factors that regulate hepatic DGK‐θ expression, we examined the role of bile acid signaling in controlling DGK‐θ gene expression. We show that chenodeoxycholic acid and GW4064 induce DGK‐θ mRNA and protein expression in a dose‐dependent manner. Reporter gene studies using 1.5 kB of the DGK‐θ promoter fused to the luciferase gene revealed that the farnesoid X receptor (FXR) increases DGK‐ θ promoter activity, and that GW4064 potentiates FXR‐dependent reporter gene activity. The induction of nuclear DGK‐θ expression is concomitant with the increase in the nuclear production of PA. Given that the nuclear receptor liver receptor homolog‐1 (LRH‐1) binds phospholipids and regulates the bile acid metabolism, we postulate that increased nuclear DGK‐θ expression may modulate cholesterol homeostasis and bile acid metabolism by controlling nuclear PA production and LRH‐1 function.