Linked Life Data

17662526

Source:http://linkedlifedata.com/resource/pubmed/id/17662526

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-8-6
pubmed:abstractText
The nuclear oxysterol receptors known as liver X receptors (LXR) are responsible for regulating genes involved in cholesterol homeostasis. Two subtypes exist, LXR-alpha and LXR-beta, both of which are expressed in the central nervous system (CNS). Activation of LXR causes an increase in mechanisms involved in cholesterol efflux, including ATP-binding cassette transporters (ABC)-A1 and ABC-G1. Although LXR agonists have been found to induce gene expression for ABC-A1 and ABC-G1 in the CNS, no functional response has been recorded. In this study, we show that an LXR agonist (TO-901317) increases protein levels of the cholesterol transporters ABC-A1 and ABC-G1, as well as the cholesterol chaperone protein apolipoprotein E (apoE). These changes are associated with a decrease in cholesterol levels from isolated cortical synaptosomal plasma membranes. LXR activation occurs in response to increased cholesterol levels in cells. However, while data exists on how LXR alter cholesterol efflux, there is no data on whether these receptors alter production of cholesterol. We found that TO-901317 increases HMG-CoA reductase activity, the rate-limiting step of cholesterol production in vivo. This finding was duplicated in an in vitro system. Although high concentrations (>1 microM) of TO-901317 were required to induce HMG-CoA reductase activity, these changes only occurred in the presence of apolipoprotein AI, suggesting that cholesterol efflux is required for this effect to occur. These data show that the LXR agonist TO-901317 is capable of reducing cholesterol in neurons of the CNS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
423
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17662526-ATP-Binding Cassette Transporters, pubmed-meshheading:17662526-Animals, pubmed-meshheading:17662526-Apolipoprotein A-I, pubmed-meshheading:17662526-Blotting, Western, pubmed-meshheading:17662526-CHO Cells, pubmed-meshheading:17662526-Central Nervous System, pubmed-meshheading:17662526-Cholesterol, pubmed-meshheading:17662526-Cricetinae, pubmed-meshheading:17662526-Cricetulus, pubmed-meshheading:17662526-DNA-Binding Proteins, pubmed-meshheading:17662526-Homeostasis, pubmed-meshheading:17662526-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:17662526-Male, pubmed-meshheading:17662526-Mice, pubmed-meshheading:17662526-Orphan Nuclear Receptors, pubmed-meshheading:17662526-RNA, Messenger, pubmed-meshheading:17662526-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:17662526-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17662526-Synaptosomes
pubmed:year
2007
pubmed:articleTitle
Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317.
pubmed:affiliation
Department of Pharmacology, ZAFES, Biocenter Niederursel, University of Frankfurt, Frankfurt, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't