Linked Life Data

6736025

Source:http://linkedlifedata.com/resource/pubmed/id/6736025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1984-7-30
pubmed:abstractText
Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34, reductase) activity was studied in cultured rat intestinal epithelial cells using 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one ( U18666A ), an inhibitor of 2,3- oxidosqualene cyclase (EC 5.4.99.7, cyclase) that causes cellular accumulation of squalene 2,3:22,23-dioxide ( Sexton , R. C., Panini , S.R., Azran , F., and Rudney , H. (1983) Biochemistry 22, 5687-5692). Treatment of cells with U18666A (5-50 ng/ml) caused a progressive inhibition of reductase activity. Further increases in the level of the drug paradoxically lessened the inhibition such that at a level of 1 microgram/ml, no inhibition of enzyme activity was observed. Cellular metabolism of squalene 2,3:22,23-dioxide to compounds with the chromatographic properties of polar sterols led to an inhibition of reductase activity that could be prevented by U18666A (1 microgram/ml). The drug was unable to prevent the inhibition of enzyme activity by 25-hydroxycholesterol or mevalonolactone, but totally abolished the inhibitory action of low density lipoproteins. Pretreatment with U18666A did not affect the ability of cells to degrade either the apoprotein or the cholesteryl ester component of low density lipoproteins. These results suggest that oxysterols derived from squalene 2,3:22,23-dioxide may act as physiological regulators of reductase and raise the possibility that the suppressive action of low density lipoproteins on reductase may be partially or wholly mediated by such endogenous oxysterols generated through incomplete inhibition of the cyclase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/25-hydroxycholesterol, http://linkedlifedata.com/resource/pubmed/chemical/3-beta-(2-(diethylamino)ethoxy)andro..., http://linkedlifedata.com/resource/pubmed/chemical/Androstenes, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxycholesterols, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases, http://linkedlifedata.com/resource/pubmed/chemical/Intramolecular Transferases, http://linkedlifedata.com/resource/pubmed/chemical/Isomerases, http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Mevalonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/lanosterol synthase, http://linkedlifedata.com/resource/pubmed/chemical/mevalonolactone
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7767-71
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by oxysterol by-products of cholesterol biosynthesis. Possible mediators of low density lipoprotein action.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.