Document Detail


Processing of cholesteryl ester from low-density lipoproteins in the rat. Hepatic metabolism and biliary secretion after uptake by different hepatic cell types.
MedLine Citation:
PMID:  2930479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Biliary secretion of the cholesteryl ester moiety of (modified) low-density lipoprotein (LDL) was examined under various experimental conditions in the rat. Human LDL or acetylated LDL (acetyl-LDL), radiolabelled with [3H]cholesteryl oleate, was administered intravenously to unanesthetized rats equipped with permanent catheters in the bile duct, duodenum and heart. LDL was cleared relatively slowly from plasma, mainly by Kupffer cells. At 3 h after injection, only 0.9% of the radioactivity was found in bile; after 12 h this value was 4.5%. Uptake of LDL by hepatocytes was stimulated by treatment of the rats with 17 alpha-ethinyloestradiol (EE; 5 mg/kg for 3 successive days); this resulted in a more rapid secretion of radioactivity into bile, 3.9% and 12.4% after 3 h and 12 h respectively. The extremely rapid uptake of acetyl-LDL via the scavenger pathway, mainly by endothelial cells, resulted in the secretion of only 2.1% of its 3H label into bile within 3 h, and 9.5% within 12 h. Radioactivity in bile was predominantly in the form of bile acids; only a small part was secreted as free cholesterol. However, the specific radioactivity of biliary cholesterol was higher than that of bile acids in all three experimental conditions. EE-treated animals did not form cholic acid from [3H]cholesteryl oleate, which was a major product of the cholesteryl oleate from LDL and acetyl-LDL in untreated rats, but formed predominantly very polar bile acids, i.e. muricholic acids. It is concluded that uptake of human LDL or acetyl-LDL by the liver of untreated rats is not efficiently coupled to biliary secretion of cholesterol (bile acids). This might be due to the anatomical localization of their principal uptake sites, the Kupffer cells and the endothelial cells respectively. Induction of LDL uptake by hepatocytes by EE treatment warrants a more efficient disposition of cholesterol from the body via bile.
Authors:
F Kuipers; J F Nagelkerke; H Bakkeren; R Havinga; T J Van Berkel; R J Vonk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  257     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-04-25     Completed Date:  1989-04-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  699-704     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile Acids and Salts / metabolism*
Bile Ducts / metabolism*
Cholesterol Esters / metabolism*
Ethinyl Estradiol / pharmacology
Humans
Lipoproteins, LDL / metabolism*
Liver / cytology,  drug effects,  metabolism*
Male
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholesterol Esters; 0/Lipoproteins, LDL; 0/acetyl-LDL; 303-43-5/cholesteryl oleate; 57-63-6/Ethinyl Estradiol
Comments/Corrections

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