Linked Life Data

18395509

Source:http://linkedlifedata.com/resource/pubmed/id/18395509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-5-27
pubmed:abstractText
P-glycoprotein, encoded by the MDR1 gene, is a drug efflux transporter that is expressed in various tissues and plays an important role in the absorption and elimination of many drugs and xenobiotics. Induction of the MDR1 gene affects drug disposition and the efficacy of drug treatment. In this study, we demonstrated that the thyroid hormone receptor (TR) induces MDR1 gene expression in a thyroid hormone (TH)-dependent manner. The 5'-upstream region of the human MDR1 gene was examined for the presence of TH-responsive elements. Luciferase-reporter gene assays revealed that the TH response region is located between -7.9 and -7.8kb upstream from the transcription start site of MDR1. The region contains two TH response clusters, one of which includes a direct repeat with a three-nucleotide spacer (DR3) and a four-nucleotide spacer DR4(I), and the other of which includes two DR4s (II and III). Mutation analyses indicated that every direct repeat has a unique contribution to the TH response. In particular, DR4(I) was shown to be the most important element. Chromatin immunoprecipitation assays revealed that TR and retinoid X receptor (RXR) bind to the TH response region, and gel mobility shift assays confirmed that one molecule of TR/RXR heterodimer binds to each of the clusters in this region, with preferential binding to the upstream one. We furthermore demonstrated that two molecules of TR/RXR could bind simultaneously to the TH response region. The order of binding affinity to the direct repeats was DR4(I)>DR4(II)>DR4(III) approximately DR3. Our results indicate that these two closely spaced TR/RXR-binding clusters are both required for the maximal induction of MDR1 gene expression mediated by TR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-0384
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
474
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82-90
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Thyroid hormone receptor mediates human MDR1 gene expression-Identification of the response region essential for gene expression.
pubmed:affiliation
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. kurose@nihs.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't