Linked Life Data

8093104

Source:http://linkedlifedata.com/resource/pubmed/id/8093104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-10-19
pubmed:abstractText
Cyclandelate (3,3,5-trimethylcyclohexanylmandelate) caused a dose-dependent decrease in the metabolism of radioiodinated low density lipoprotein [125I-LDL] by J774 mouse macrophages. This was probably an indirect effect due to the inhibition of cholesterol esterification by the cells rather than a direct one on the interaction of LDL with its receptor, since no inhibition was seen in cells which had been cholesterol-depleted by prior incubation with lipoprotein-depleted serum for 48 hr. Cyclandelate also inhibited immediately de novo synthesis of cholesterol from [1-14C]acetate in J774 cells, suggesting a direct action of the drug on an enzyme of the cholesterol biosynthetic pathway. The drug was an efficient inhibitor of hamster and rat intestinal acylcoenzyme A: cholesterol acyltransferase (ACAT) activity in vitro with an IC50 of 20 microM. Addition of cyclandelate to the diet of meal-fed rats caused a marked inhibition of the rate of appearance of dietary [4-14C]cholesterol in the plasma. A nonhydrolysable ether analogue of cyclandelate, benzyl3,3,5-trimethylcyclohexanol, was prepared to compare hepatic and extrahepatic actions of the two molecules. The analogue inhibited cholesterol esterification in J774 cells, transformed human macrophages U937 and human umbilical vein endothelial cells with an IC50 of 20 microM and had effects similar to those of cyclandelate on 125I-LDL metabolism in J774 cells. Differences between the analogue and cyclandelate were seen in hepatocytes and hepatic microsomal fractions, where preincubation with the analogue inhibited cholesterol esterification in both systems while cyclandelate had no inhibitory action in either. Consequently, preincubation of rat hepatocytes with benzyl3,3,5-trimethylcyclohexanol for 17 hr caused a marked decrease in the binding of 125I-LDL to the cells, whereas binding to cells preincubated with cyclandelate was the same as to control cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
915-22
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
The effects of two acylcoenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cyclandelate and a non-hydrolysable ether analogue, benzyl3,3,5-trimethylcyclohexanol on low density lipoprotein metabolism in macrophages and hepatocytes.
pubmed:affiliation
Department of Biochemistry, University of Nottingham Medical School, U.K.
pubmed:publicationType
Journal Article