Source:http://linkedlifedata.com/resource/pubmed/id/21464203
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2011-5-16
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| pubmed:abstractText |
It is claimed that apoA-I expression is repressed in mice by cholic acid (CA) and its taurine conjugate, taurocholic acid (TCA) via farnesoid X receptor (FXR) activation. We measured apoA-I expression in mice, hamsters, and rats treated with highly potent and selective synthetic FXR agonists or with TCA. All of the synthetic agonists bound to FXR with high affinity in a scintillation proximity assay. However, TCA did not compete with the radioligand up to the highest concentration used (100 ?M). The C-site regulatory region of apoA-I, through which FXR has been reported to regulate its expression, is completely conserved across the species investigated. In both male and female human apoA-I-transgenic mice, we reproduced the previously reported strong inhibition of human apoA-I expression upon treatment with the typical supraphysiological dose of TCA used in such studies. However, in contrast to some previous reports, TCA did not repress murine apoA-I expression in the same mice. Also, more-potent and -selective FXR agonists did not affect human or murine apoA-I expression in this model. In LDL receptor-deficient mice and Golden Syrian hamsters, selective FXR agonists did not affect apoA-I expression, whereas in Wistar rats, some even increased apoA-I expression. In conclusion, selective FXR agonists do not repress apoA-I expression in rodents. Repression of human apoA-I expression by TCA in transgenic mice is probably mediated through FXR-independent mechanisms.
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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/Apolipoprotein A-I,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Taurocholic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/farnesoid X-activated receptor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0022-2275
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
52
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1188-99
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| pubmed:meshHeading |
pubmed-meshheading:21464203-Animals,
pubmed-meshheading:21464203-Apolipoprotein A-I,
pubmed-meshheading:21464203-Binding Sites,
pubmed-meshheading:21464203-Conserved Sequence,
pubmed-meshheading:21464203-Cricetinae,
pubmed-meshheading:21464203-Female,
pubmed-meshheading:21464203-Gene Expression Regulation,
pubmed-meshheading:21464203-Humans,
pubmed-meshheading:21464203-Liver,
pubmed-meshheading:21464203-Male,
pubmed-meshheading:21464203-Mesocricetus,
pubmed-meshheading:21464203-Mice,
pubmed-meshheading:21464203-Mice, Inbred C57BL,
pubmed-meshheading:21464203-Mice, Transgenic,
pubmed-meshheading:21464203-Promoter Regions, Genetic,
pubmed-meshheading:21464203-Protein Binding,
pubmed-meshheading:21464203-RNA, Messenger,
pubmed-meshheading:21464203-Rats,
pubmed-meshheading:21464203-Rats, Wistar,
pubmed-meshheading:21464203-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:21464203-Scintillation Counting,
pubmed-meshheading:21464203-Species Specificity,
pubmed-meshheading:21464203-Taurocholic Acid
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| pubmed:year |
2011
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| pubmed:articleTitle |
Studies in mice, hamsters, and rats demonstrate that repression of hepatic apoA-I expression by taurocholic acid in mice is not mediated by the farnesoid-X-receptor.
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| pubmed:affiliation |
Department of Metabolic Diseases, F. Hoffmann-La Roche AG, 4070 Basel, Switzerland. christophe.gardes@roche.com
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| pubmed:publicationType |
Journal Article
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