Linked Life Data

9278389

Source:http://linkedlifedata.com/resource/pubmed/id/9278389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
1997-10-2
pubmed:abstractText
Since elevated concentrations of plasma high density lipoprotein (HDL) and its major apolipoprotein (apo), apoA-I, confer protection against atherosclerosis, considerable research efforts have focussed on the identification of factors regulating apoA-I gene expression in an attempt to increase its production. Nuclear receptors are interesting candidates because they are transcription factors whose activity is ligand-dependent. In the present study we identified the orphan receptor RORalpha1 as an activator of apoA-I gene transcription. In apoA-I-expressing intestinal Caco-2 cells, overexpression of the RORalpha1, but not the RORalpha2 or RORalpha3 isoforms, increased rat apoA-I gene transcription. Deletion and site-directed mutagenesis experiments identified a functional ROR-responsive element (RORE) in the rat and mouse apoA-I gene promoters, which overlaps with the TATA box. Gel shift experiments indicated that this RORE binds the RORalpha1 isoform, but not the RORalpha2 or RORalpha3 isoforms. Furthermore, compared with wild type mice, apoA-I mRNA levels were significantly lower in small intestines of staggerer mice homozygous for a deletion in the RORalpha gene. In addition, reverse transcriptase-polymerase chain reaction analysis revealed the expression of RORalpha in small intestinal epithelium and in Caco-2 cells. These data indicate a novel, physiological role for RORalpha1 in the regulation of genes involved in lipid and lipoprotein metabolism and possibly in the development of metabolic diseases, such as atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22401-4
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Transcriptional regulation of apolipoprotein A-I gene expression by the nuclear receptor RORalpha.
pubmed:affiliation
Département d'Athérosclérose, U.325 INSERM, Institut Pasteur de Lille and Université de Lille II, 1 Rue Calmette, 59019 Lille, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't