Document Detail

Glibenclamide acts as an inhibitor of acyl-CoA:cholesterol acyltransferase enzyme.
MedLine Citation:
PMID:  11032738     Owner:  NLM     Status:  MEDLINE    
Sulfonylureas are used in the treatment of non-insulin-dependent diabetes mellitus. Little is known, however, about their effects on cholesterol metabolism. We tested in the present study the effects of glibenclamide (GB) on cholesterol esterification (CE) in macrophage-derived cells. GB inhibited intracellular accumulation of CE induced by acetylated LDL or oxidized LDL in J774 cells, but no such effect on total cholesterol, suggesting that the target of GB was acyl-CoA:cholesterol acyltransferase (ACAT). In the cell-free reconstitution ACAT assay, GB inhibited the ACAT activity with an IC(50) value of 20 microM. Furthermore, GB effectively inhibited the ACAT activity of PMA-stimulated THP-1 cells to the undifferentiated level of THP-1. In the whole-cell ACAT assay using CHO cells overexpressed with ACAT-1 or ACAT-2, GB inhibited the activity of both isozymes with similar potency. Our in vitro data suggest that sulfonylurea could be a potential seed for a new generation of ACAT inhibitors.
N Ohgami; A Kuniyasu; K Furukawa; A Miyazaki; H Hakamata; S Horiuchi; H Nakayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  277     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-06     Completed Date:  2000-11-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  417-22     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Ohe-Honmachi, Kumamoto, 862-0973, Japan.
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MeSH Terms
Anilides / chemistry,  pharmacology
Aniline Compounds / chemistry,  pharmacology
CHO Cells
Cell Line
Cell-Free System
Cholesterol / metabolism
Cyclohexanes / chemistry,  pharmacology
Dose-Response Relationship, Drug
Glyburide / chemistry,  pharmacology*
Hypoglycemic Agents / pharmacology*
Inhibitory Concentration 50
Isoenzymes / metabolism
L-Lactate Dehydrogenase / metabolism
Lipoproteins, LDL / pharmacology
Macrophages / drug effects
Sterol O-Acyltransferase / antagonists & inhibitors*,  metabolism
Tetradecanoylphorbol Acetate / pharmacology
Reg. No./Substance:
0/Anilides; 0/Aniline Compounds; 0/Cyclohexanes; 0/Hypoglycemic Agents; 0/Isoenzymes; 0/Lipoproteins, LDL; 0/NTE 122; 0/acetyl-LDL; 0/oxidized low density lipoprotein; 10238-21-8/Glyburide; 114289-47-3/PD 128042; 16561-29-8/Tetradecanoylphorbol Acetate; 57-88-5/Cholesterol; EC Dehydrogenase; EC O-Acyltransferase

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

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