Document Detail

ApoB-100 secretion by HepG2 cells is regulated by the rate of triglyceride biosynthesis but not by intracellular lipid pools.
MedLine Citation:
PMID:  8857918     Owner:  NLM     Status:  MEDLINE    
Triglycerides (TGs), cholesteryl esters (CEs), cholesterol, and phosphatidylcholine have been independently proposed as playing regulatory roles in apoB-100 secretion; the results depended on the cellular model used. In this study, we reinvestigate the role of lipids in apoB-100 production in HepG2 cells and in particular, we clarify the respective roles of intracellular mass and the biosynthesis of lipids in the regulation of apoB-100 production. In a first set of experiments, the pool size of cholesterol, CEs, and TGs was modulated by a 3-day treatment with either lipid precursors or inhibitors of enzymes involved in lipid synthesis. We used simvastatin (a hydroxymethylglutaryl coenzyme A reductase inhibitor), 58-035 (an acyl coenzyme A cholesterol acyltransferase inhibitor), 5-tetradecyloxy-2-furancarboxylic acid (TOFA, an inhibitor of fatty acid synthesis), and oleic acid. The secretion rate of apoB-100 was not affected by the large modulation of lipid mass induced by these various pre-treatments. In a second set of experiments, the same lipid modulators were added during a 4-hour labeling period. Simvastatin and 58-035 inhibited cholesterol and CE synthesis without affecting apoB-100 secretion. By contrast, treatment of HepG2 cells with TOFA resulted in the inhibition of TG synthesis and apoB-100 secretion. This effect was highly specific for apoB-100 and was reversed by adding oleic acid, which stimulated both TG synthesis and apoB-100 secretion. Moreover, a combination of oleic acid and 58-035 inhibited CE biosynthesis and increased both TG synthesis and apoB-100 secretion. These results show that in HepG2 cells TG biosynthesis regulates apoB-100 secretion, whereas the rate of cholesterol or CE biosynthesis has no effect.
F Benoist; T Grand-Perret
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  16     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-11-20     Completed Date:  1996-11-20     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1229-35     Citation Subset:  IM    
Laboratoire Glaxo Wellcome, Centre de Recherche, Les Ulis, France.
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MeSH Terms
Antilipemic Agents / pharmacology
Apolipoproteins B / secretion*
Carcinoma, Hepatocellular
Enzyme Inhibitors / pharmacology
Furans / pharmacology
Lipid Metabolism*
Lovastatin / analogs & derivatives,  pharmacology
Triglycerides / biosynthesis*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antilipemic Agents; 0/Apolipoproteins B; 0/Enzyme Inhibitors; 0/Furans; 0/Triglycerides; 54857-86-2/5-(tetradecyloxy)-2-furancarboxylic acid; 75330-75-5/Lovastatin; 79902-63-9/Simvastatin

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