Submitted on January 23, 2008
Revised on June 11, 2008
Accepted on June 19, 2008
CYP4F3B is induced by PGA1 in human liver cells: A regulation of the 20-hete synthesis
Joseph Antoun, Sophie Goulitquer, Yolande Amet, Yvonne Dréano, Jean-Pierre Salaun, Laurent Corcos, and Emmanuelle Plée-Gautier
Biochimie EA-948, Faculté de Médecine de Brest, Brest 29238
Corresponding Author: emmanuelle.plee-gautier{at}univ-brest.fr
The regulation of the human liver-specific cytochrome P450 4F3B (CYP4F3B) isoform, a splice variant of the CYP4F3 gene with strong substrate specificity for long chain fatty acids, is yet an unsolved question. This report provides the first evidence that CYP4F3B is uniquely induced by prostaglandin A1 (PGA1) in human hepatocyte-like HepaRG cells, and leads to the synthesis of 20-HETE. Real time PCR, immunoblot analysis with a specific anti-peptide antibody and determination of fatty acid omega-hydroxylase activity demonstrate that PGA1 treatment strongly increases expression of CYP4F3B. This induction drives the production of 20-HETE (19-fold increase). SiRNA-mediated-silencing of CYP4F3 suppresses both 20-HETE synthesis and PGA1 induced 20-HETE production. Taken together, these results provide evidence that CYP4F3B is the key enzyme to produce 20-HETE by -hydroxylation of arachidonic acid in liver cells. Since 20-HETE is a potent activator of PPAR and an important inflammatory mediator, CYP4F3B may exert important functions in lipid homeostasis and in inflammatory diseases.
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