Linked Life Data

20829431

Source:http://linkedlifedata.com/resource/pubmed/id/20829431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-18
pubmed:abstractText
Organic anion transporters (OATs) are anion exchangers that transport small hydrophilic anions and diuretics, antibiotics, nonsteroidal anti-inflammatory drugs, antiviral nucleoside analogs, and antitumor drugs across membrane barriers of epithelia of diverse organs. Three OATs are present in human liver: OAT2, OAT5, and OAT7. Given that hepatocyte nuclear factor-1? (HNF-1?) has previously been shown to regulate the expression of several hepatocellular transporter genes, we investigated whether the liver-specific human OAT genes are also regulated by HNF-1?. Short interfering RNAs targeting HNF-1? reduced endogenous expression of OAT5 and OAT7, but not OAT2, in human liver-derived Huh7 cells. Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1? in HepG2 cells. Two putative HNF-1? binding elements in the proximal OAT5 promoter, located at nucleotides -68/-56 and -173/-160, and one element in the OAT7 promoter, located at nucleotides -14/-2 relative to the transcription start site, were shown to bind HNF-1? in electromobility shift assays, and these promoter regions also interacted with HNF-1? in chromatin immunoprecipitation assays. A correlation between HNF-1? and OAT5 (r = 0.134, P < 0.05) or OAT7 (r = 0.461, P < 0.001) mRNA expression levels in surgical liver biopsies from 75 patients further supported an important role of HNF-1? in the regulation of OAT gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1079-87
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The human organic anion transporter genes OAT5 and OAT7 are transactivated by hepatocyte nuclear factor-1? (HNF-1?).
pubmed:affiliation
Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, Zurich, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't