Linked Life Data

15353128

Source:http://linkedlifedata.com/resource/pubmed/id/15353128

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-8
pubmed:abstractText
In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1001-0602
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-23
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15353128-Arteriosclerosis, pubmed-meshheading:15353128-Base Sequence, pubmed-meshheading:15353128-Cell Line, pubmed-meshheading:15353128-Cholesterol, LDL, pubmed-meshheading:15353128-Cholesterol Esters, pubmed-meshheading:15353128-Dexamethasone, pubmed-meshheading:15353128-Enzyme Inhibitors, pubmed-meshheading:15353128-Foam Cells, pubmed-meshheading:15353128-Gene Expression Regulation, pubmed-meshheading:15353128-Glucocorticoids, pubmed-meshheading:15353128-Humans, pubmed-meshheading:15353128-Macrophages, pubmed-meshheading:15353128-Molecular Sequence Data, pubmed-meshheading:15353128-Promoter Regions, Genetic, pubmed-meshheading:15353128-RNA, Messenger, pubmed-meshheading:15353128-Receptors, Glucocorticoid, pubmed-meshheading:15353128-Response Elements, pubmed-meshheading:15353128-Sterol O-Acyltransferase, pubmed-meshheading:15353128-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone.
pubmed:affiliation
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Rd, Shanghai 200031, China.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't