Source:http://linkedlifedata.com/resource/pubmed/id/10867000
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
37
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| pubmed:dateCreated |
2000-10-13
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| pubmed:abstractText |
Fibrates are a group of hypolipidemic agents that efficiently lower serum triglyceride levels by affecting the expression of many genes involved in lipid metabolism. These effects are exerted via the peroxisome proliferator-activated receptor alpha (PPARalpha). In addition, fibrates also lower serum cholesterol levels, suggesting a possible link between the PPARalpha and cholesterol metabolism. Bile acid formation represents an important pathway for elimination of cholesterol, and the sterol 12alpha-hydroxylase is a branch-point enzyme in the bile acid biosynthetic pathway, which determines the ratio of cholic acid to chenodeoxycholic acid. Treatment of mice for 1 week with the peroxisome proliferator WY-14,643 or fasting for 24 h both induced the sterol 12alpha-hydroxylase mRNA in liver. Using the PPARalpha knockout mouse model, we show that the induction by both treatments was dependent on the PPARalpha. A reporter plasmid containing a putative peroxisome proliferator-response element (PPRE) identified in the rat sterol 12alpha-hydroxylase promoter region was activated by treatment with WY-14,643 in HepG2 cells, being dependent on co-transfection with a PPARalpha expression plasmid. The rat 12alpha-hydroxylase PPRE bound in vitro translated PPARalpha and retinoid X receptor alpha, albeit weakly, in electrophoretic mobility shift assay. Treatment of wild-type mice with WY-14,643 for 1 week resulted in an increased relative amount of cholic acid, an effect that was abolished in the PPARalpha null mice, verifying the functionality of the PPRE in vivo.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid 12-alpha-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/pirinixic acid
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
|
| pubmed:volume |
275
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
28947-53
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10867000-Animals,
pubmed-meshheading:10867000-Base Sequence,
pubmed-meshheading:10867000-Bile Acids and Salts,
pubmed-meshheading:10867000-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10867000-Gene Expression Regulation,
pubmed-meshheading:10867000-Male,
pubmed-meshheading:10867000-Mice,
pubmed-meshheading:10867000-Molecular Sequence Data,
pubmed-meshheading:10867000-Promoter Regions, Genetic,
pubmed-meshheading:10867000-Pyrimidines,
pubmed-meshheading:10867000-RNA, Messenger,
pubmed-meshheading:10867000-Rats,
pubmed-meshheading:10867000-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10867000-Receptors, Retinoic Acid,
pubmed-meshheading:10867000-Response Elements,
pubmed-meshheading:10867000-Retinoid X Receptors,
pubmed-meshheading:10867000-Steroid 12-alpha-Hydroxylase,
pubmed-meshheading:10867000-Steroid Hydroxylases,
pubmed-meshheading:10867000-Transcription Factors
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| pubmed:year |
2000
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| pubmed:articleTitle |
The peroxisome proliferator-activated receptor alpha (PPARalpha) regulates bile acid biosynthesis.
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| pubmed:affiliation |
Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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