Linked Life Data

19156545

Source:http://linkedlifedata.com/resource/pubmed/id/19156545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-3-24
pubmed:abstractText
High-density lipoprotein (HDL) particles play a critical role in cholesterol metabolism. The hepatic scavenger receptor class B type I (SR-B1) binds HDL particles for mediating reverse cholesterol transport (RCT), thus lowering the risk of atherosclerosis. Thiazolidinediones (TZDs), known to have potent enhancing effects on insulin sensitivity, have been developed for the treatment of non-insulin-dependent diabetes mellitus. They are a high-affinity ligand for the peroxisome proliferator-activated receptor gamma (PPAR-gamma), which belongs to a nuclear receptor superfamily. In this study, we examined the effects of thiazolidinedione PPAR-gamma on hepatic SR-B1 gene expression in human hepatoma G2 cell-line (HepG2). Results showed that hepatic SR-B1 mRNA and protein were increased on exposure to thiazolidinediones. Transcriptional activity of human SR-B1 (hSR-B1) gene paralleled the endogenous expression of the gene and was dependent on the dose of thiazolidinediones. We investigated the influence on the promoter activity of vector expressing PPAR and retinoid X receptor (RXR), cotransfected into the HepG2 cells along with SR-B1 promoter-reporter gene constructs. PPAR-gamma and RXR sufficiently induced the SR-B1 promoter activity in the HepG2 cells. Chromatin immunoprecipitation (ChIP) assay confirmed the binding of the PPAR-gamma to the SR-B1 promoter region. The mutagenesis of this binding site abolished the ability of the thiazolidinediones or PPARs to stimulate promoter activity. Together, these results indicate that the stimulation of SR-B1 expression in the liver is mediated in part by activation of the PPAR-gamma and RXR, and raise the possibility that this stimulation using thiazolidinediones conditions provides a protective mechanism for accelerated atherosclerosis in diabetes mellitus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1355-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-42
pubmed:dateRevised
2010-6-24
pubmed:meshHeading
pubmed-meshheading:19156545-Binding Sites, pubmed-meshheading:19156545-Carcinoma, Hepatocellular, pubmed-meshheading:19156545-Cell Line, Tumor, pubmed-meshheading:19156545-Cholesterol Esters, pubmed-meshheading:19156545-DNA, pubmed-meshheading:19156545-Gene Expression Regulation, pubmed-meshheading:19156545-Hepatocytes, pubmed-meshheading:19156545-Humans, pubmed-meshheading:19156545-Liver Neoplasms, pubmed-meshheading:19156545-Mutagenesis, pubmed-meshheading:19156545-PPAR gamma, pubmed-meshheading:19156545-Promoter Regions, Genetic, pubmed-meshheading:19156545-RNA, Messenger, pubmed-meshheading:19156545-Retinoid X Receptors, pubmed-meshheading:19156545-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19156545-Scavenger Receptors, Class B, pubmed-meshheading:19156545-Thiazolidinediones, pubmed-meshheading:19156545-Transfection
pubmed:year
2009
pubmed:articleTitle
Human scavenger receptor class B type 1 is regulated by activators of peroxisome proliferators-activated receptor-gamma in hepatocytes.
pubmed:affiliation
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't