Linked Life Data

2745447

Source:http://linkedlifedata.com/resource/pubmed/id/2745447

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1989-8-18
pubmed:abstractText
We have examined the effects of ketoconazole, a drug which inhibits enzymes involved in cholesterol biosynthesis and metabolism, on the suppressive effects of serum lipoproteins and 25-hydroxycholesterol on low density lipoprotein (LDL) receptor gene promoter activity. A LDL receptor promoter-chloramphenicol acetyltransferase (CAT) fusion gene construct (pLDLR-CAT 6500) was transfected into JEG-3 choriocarcinoma cells, and the transfected cells were cultured in the absence or presence of serum, LDL, or serum and 25-hydroxycholesterol. Serum, LDL, and serum + 25-hydroxycholesterol reduced chloramphenicol acetyltransferase activity in cells transfected with pLDLR-CAT 6500, whereas these treatments had no effect upon enzyme activity in cells transfected with a control construct (pSV2CAT). Ketoconazole (50 microM) overcame the effects of serum and LDL on suppression of pLDLR-CAT 6500 expression, but could not override the combination of serum + 25-hydroxycholesterol. Ketoconazole had no significant effect on expression of pSV2CAT. The drug inhibited cholesterol side chain cleavage enzyme in the cells, but appeared to have no impact on the ability of cells to take up LDL-carried lipids. Our observations are consistent with the idea that serum lipoprotein cholesterol is metabolized to an effector substance which acts to suppress LDL receptor gene transcription. The generation of this effector seems to be sensitive to ketoconazole.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12352-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Control of low density lipoprotein receptor gene promoter activity. Ketoconazole inhibits serum lipoprotein but not oxysterol suppression of gene transcription.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.