Document Detail


Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and of incorporation of acetate into cholesterol in homozygous hypercholesterolemic fibroblasts by ferritin-low density lipoprotein conjugates.
MedLine Citation:
PMID:  205253     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conjugates of ferritin with low density lipoproteins (LDL) were prepared and separated by sucrose gradient centrifugation. These conjugates, at cholesterol concentration of 100--132 microgram/ml, caused a greater than 90% suppression of hydroxymethylglutaryl coenzyme A reductase activity and of acetate incorporation into cholesterol in cultured skin fibroblasts from a normal subject as well as from a subject with homozygous familial hypercholesterolemia. The half maximal inhibition concentration was approx. 10 microgram/ml cholesterol for LDL and ferritin . (LDL)2 and 5 microgram/ml for (ferritin)2 . LDL in both cell lines. In contrast, native low density lipoproteins have only a minimal inhibitory effect in homozygous cells. The ability of the conjugates to stimulate the incorporation of oleate into cholesteryl esters was also equal in the two cell lines, although the conjugates were only 10% as active as low density lipoproteins in the normal cells. LDL reduced the ferritin . (LDL)2-mediated suppression of hydroxymethylglutaryl-CoA reductase activity in homozygous cells while ferritin . (LDL)2 reduced the LDL-mediated stimulation of cholesteryl ester formation in normal cells.
Authors:
C H Fung; C H Wang; A K Khachadurian
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  528     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1978 Mar 
Date Detail:
Created Date:  1978-06-12     Completed Date:  1978-06-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  445-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetates / metabolism*
Cholesterol / biosynthesis*
Ferritins / pharmacology*
Fibroblasts / drug effects,  metabolism
Homozygote
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Hypercholesterolemia / metabolism*
Kinetics
Lipoproteins, LDL / pharmacology*
Chemical
Reg. No./Substance:
0/Acetates; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lipoproteins, LDL; 57-88-5/Cholesterol; 9007-73-2/Ferritins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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