Document Detail


CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis.
MedLine Citation:
PMID:  18566475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-hydroxy-eicosatetraenoic acids (HETEs). Real time PCR, immunoblot analysis with a specific antipeptide 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 omega-hydroxylation of arachidonic acid in liver cells. Since 20-HETE is a potent activator of PPARalpha and an important inflammatory mediator, CYP4F3B may exert important functions in lipid homeostasis and in inflammatory diseases.
Authors:
Joseph Antoun; Sophie Goulitquer; Yolande Amet; Yvonne Dreano; Jean-Pierre Salaun; Laurent Corcos; Emmanuelle Plée-Gautier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-19
Journal Detail:
Title:  Journal of lipid research     Volume:  49     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-15     Completed Date:  2008-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2135-41     Citation Subset:  IM    
Affiliation:
Equipe d'Accueil-948, Faculté de Médecine, Université de Bretagne Occidentale, 29238 Brest, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cattle
Cytochrome P-450 Enzyme System / biosynthesis*,  genetics
Dose-Response Relationship, Drug
Enzyme Induction / drug effects
Gene Deletion
Gene Expression Regulation, Enzymologic / drug effects
Gene Silencing
Glucuronides / metabolism
Hepatocytes / drug effects*,  enzymology,  metabolism*
Humans
Hydroxyeicosatetraenoic Acids / biosynthesis*
Prostaglandins A / pharmacology*
RNA, Small Interfering / genetics,  metabolism
Time Factors
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Glucuronides; 0/Hydroxyeicosatetraenoic Acids; 0/Prostaglandins A; 0/RNA, Small Interfering; 14152-28-4/prostaglandin A1; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.13.30/CYP4F3 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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