Document Detail


Changes in the expression of genes related to bile acid synthesis and transport by the rat liver during hepatocarcinogenesis.
MedLine Citation:
PMID:  15853769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The relationship between BA (bile acid) secretion (measured by GC-MS) and the expression of genes (measured by reverse transcription real-time PCR) involved in liver BA transport and metabolism was investigated at 20 and 32 weeks during rat hepatocarcinogenesis. A progressive loss of mRNA for transporters (more marked for Ntcp, Bsep and Mrp2 than for Oatp1/Oatp1a1, Oatp2/Oatp1a4 and Oatp4/Oatp1b2) was found. The mRNA levels of Cyp7a1 and the nuclear receptors FXR (farnesoid X receptor), SHP (small heterodimer partner) and FTF (alpha-fetoprotein transcription factor) were not modified, whereas those of Cyp8b1 were enhanced and those of Cyp27 were reduced. Biliary secretion of CA (cholic acid) remained unchanged, whereas that of CDCA (chenodeoxycholic acid) and other non-C(12)-hydroxylated BAs was diminished. The re-appearance of 'flat-BAs' (mainly allo-BAs at 20 weeks and Delta(4)-unsaturated-BAs at 32 weeks) probably reflects the progressive decrease observed in the expression of 3-oxo-Delta(4)-steroid 5beta-reductase, together with the maintenance of steroid 5alpha-reductase type I. A significant correlation between the 5alpha-reductase/5beta-reductase ratio and bile output of 'flat-BAs' was found. In conclusion, during rat hepatocarcinogenesis, the expression of transporters/enzymes responsible for BA homoeostasis is changed due to mechanisms other than those controlled by FXR/SHP/FTF. These modifications result in the re-appearance of 'flat-BAs', together with an increased CA/CDCA ratio in bile.
Authors:
Maria J Monte; Maria Fernandez-Tagarro; Rocio I R Macias; Felipe Jimenez; Francisco Gonzalez-San Martin; Jose J G Marin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  109     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-21     Completed Date:  2005-09-21     Revised Date:  2009-04-16    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  199-207     Citation Subset:  IM    
Affiliation:
Laboratory of Experimental Hepatology and Drug Targeting, Department of Physiology and Pharmacology, University of Salamanca, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile Acids and Salts / biosynthesis*
Biological Transport
Cholestenone 5 alpha-Reductase / genetics
Cytochrome P-450 CYP27A1
DNA-Binding Proteins / genetics
Gene Expression
Liver / metabolism*
Liver Neoplasms / metabolism*
Male
Neoplasms, Experimental
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear / genetics
Reverse Transcriptase Polymerase Chain Reaction
Steroid 12-alpha-Hydroxylase / genetics
Steroid Hydroxylases / genetics
Transcription Factors / genetics
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/DNA-Binding Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors; 0/farnesoid X-activated receptor; 0/fetoprotein transcription factor; 0/nuclear receptor subfamily 0, group B, member 2; EC 1.14.-/Cytochrome P-450 CYP27A1; EC 1.14.-/Steroid 12-alpha-Hydroxylase; EC 1.14.-/Steroid Hydroxylases; EC 1.3.1.22/Cholestenone 5 alpha-Reductase

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