Document Detail

Ezetimibe inhibits expression of acid sphingomyelinase in liver and intestine.
MedLine Citation:
PMID:  19777283     Owner:  NLM     Status:  MEDLINE    
Ezetimibe inhibits cholesterol absorption in the intestine. Sphingomyelin has strong interactions with cholesterol. We investigated the effects of ezetimibe on Sphingomyelinase (SMase) expression in intestine and liver. After feeding rats with ezetimibe (5 mg/kg per day) for 14 days, acid SMase activities in the liver and in the proximal part of small intestine were reduced by 34 and 25%, respectively. Alkaline SMase (alk-SMase) was increased in the proximal part of the small intestine. Administration of lower doses of ezetimibe reduced acid SMase only in the liver by 14% (P < 0.05). In cell culture studies, ezetimibe decreased acid SMase activity in Hep G2 and Caco-2 cells dose-dependently. The reductions were more rapid for Hep G2 cells than for Caco-2 cells. Western blot showed that acid SMase protein was decreased in both Hep G2 and Caco-2 cells by 100 microM ezetimibe. The SM content was increased in Hep G2 cells but not Caco-2 cells, and total cholesterol content was increased in both cell lines 24 h after stimulation with 100 microM ezetimibe. Mevastatin, the inhibitor of cholesterol synthesis, induced a mild increase in acid SMase activity in Hep G2 cells but not Caco-2 cells. Following the reduction of acid SMase, ezetimibe at high dose slightly increased alk-SMase activity. In conclusion, the study demonstrates an inhibitory effect of ezetimibe on acid SMase activity and expression in both liver and intestine.
Yajun Cheng; Fuli Liu; Jun Wu; Yao Zhang; Ake Nilsson; Rui-Dong Duan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-24
Journal Detail:
Title:  Lipids     Volume:  44     ISSN:  1558-9307     ISO Abbreviation:  Lipids     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2010-01-29     Completed Date:  2010-08-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  897-906     Citation Subset:  IM    
Gastroenterology and Nutrition Lab, BMC, B11, Institution of Clinical Sciences, Lund University, 221 84, Lund, Sweden.
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MeSH Terms
Azetidines / administration & dosage,  pharmacology*
Caco-2 Cells
Cell Line, Tumor
Gene Expression Regulation, Enzymologic / drug effects
Intestine, Small / drug effects,  enzymology*
Liver / drug effects,  enzymology*
Phosphodiesterase Inhibitors / pharmacology*
Rats, Sprague-Dawley
Sphingomyelin Phosphodiesterase / antagonists & inhibitors*,  biosynthesis*
Reg. No./Substance:
0/Azetidines; 0/Phosphodiesterase Inhibitors; 163222-33-1/ezetimibe; EC Phosphodiesterase

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

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