| pubmed-article:18794335 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0021853 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0023884 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0059563 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0032214 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0600138 | lld:lifeskim |
| pubmed-article:18794335 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18794335 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:18794335 | pubmed:dateCreated | 2009-1-1 | lld:pubmed |
| pubmed-article:18794335 | pubmed:abstractText | CYP3A4 is an important xenobiotic metabolizing enzyme. We previously found that CYP2C55 is highly up-regulated in Cyp3a(-/-) mice. Here, we have further investigated the mechanism of regulation of CYP2C55 and other detoxifying systems in Cyp3a(-/-) mice. Induction studies with prototypical inducers demonstrated an important role for the nuclear receptors PXR and CAR in the up-regulation of CYP2C55. Subsequent diet-switch experiments revealed that food-derived xenobiotics are primarily responsible for the increased induction of CYP2C55, as well as of several other primary detoxifying systems in Cyp3a(-/-) mice. Our data suggest that CYP3A normally metabolizes food-derived activators of PXR and/or CAR, explaining the increased levels of such activators in Cyp3a(-/-) mice and subsequent up-regulation of a range of detoxifying systems. Interestingly, our studies with tissue-specific CYP3A4 transgenic Cyp3a(-/-) mice revealed that not only hepatic but also intestinal expression of CYP3A4 could reduce the hepatic expression of detoxifying systems to near wild-type levels. Apparently, intestinal CYP3A4 can limit the hepatic exposure to food-derived activators of nuclear receptors, thereby regulating the expression of a range of detoxifying systems in the liver. This broad biological effect further emphasizes the importance of intestinal CYP3A activity and could have profound implications for the prediction of drug exposure. | lld:pubmed |
| pubmed-article:18794335 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18794335 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18794335 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18794335 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18794335 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18794335 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:18794335 | pubmed:issn | 1530-6860 | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:SchinkelAlfre... | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:WagenaarElsE | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:van... | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:van der... | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:van... | lld:pubmed |
| pubmed-article:18794335 | pubmed:author | pubmed-author:RooswinkelRog... | lld:pubmed |
| pubmed-article:18794335 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18794335 | pubmed:volume | 23 | lld:pubmed |
| pubmed-article:18794335 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18794335 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18794335 | pubmed:pagination | 224-31 | lld:pubmed |
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| pubmed-article:18794335 | pubmed:meshHeading | pubmed-meshheading:18794335... | lld:pubmed |
| pubmed-article:18794335 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:18794335 | pubmed:articleTitle | Intestinal cytochrome P450 3A plays an important role in the regulation of detoxifying systems in the liver. | lld:pubmed |
| pubmed-article:18794335 | pubmed:affiliation | Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. | lld:pubmed |
| pubmed-article:18794335 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18794335 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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