Linked Life Data

15210833

Source:http://linkedlifedata.com/resource/pubmed/id/15210833

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-9-17
pubmed:abstractText
In vitro inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase causes the suppression of liver X receptor (LXR) activity. Because LXR regulates the expression of ATP-binding cassette transporter (ABC) A1, which is involved in the high-density lipoprotein-related reverse cholesterol transport pathway, we examined the effects of an HMG-CoA reductase inhibitor pravastatin on ABCA1 expression in vitro and in vivo. Pravastatin (10 microM) significantly reduced the transcript levels of murine ABCA1 gene by 35% in RAW264.7 macrophages under a lipoprotein-deficient condition. The inhibition was due to the decreased mevalonic acid production because addition of exogenous mevalonic acid restored ABCA1 mRNA levels. In addition, cholesterol and 22(R)-hydroxycholesterol thoroughly blunted the inhibition. Furthermore, pravastatin did not decrease ABCA1 mRNA and protein levels in HepG2 hepatocytes even in the absence of exogenous LXR agonists. Oral dosing of pravastatin (0.1% concentration in drinking water) for 24 h or 2 weeks to mice did not decrease ABCA1 mRNA and protein levels in the liver and leukocytes. Interestingly, pravastatin significantly increased both hepatic and leukocyte LXRalpha mRNA levels. Thus, although HMG-CoA reductase inhibitors suppress ABCA1 mRNA expression in the absence of LXR agonists, in vivo inhibition of HMG-CoA reductase is unlikely to cause such suppression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
311
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
420-5
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effects of pravastatin on the expression of ATP-binding cassette transporter A1.
pubmed:affiliation
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical School, Tochigi 329-0498, Japan.
pubmed:publicationType
Journal Article