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Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine.

Cheng, Yajun LU ; Liu, Fuli LU ; Wu, Jun LU ; Zhang, Yao LU ; Nilsson, Åke LU and Duan, Rui-Dong LU (2009) In Lipids 44(10). p.897-906
Abstract
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... (More)
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 muM 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 muM 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholesterol, Hep G2 cells, Rat, Sphingomyelin, Liver, Intestine, Caco-2 cells, Ezetimibe, Acid sphingomyelinase
in
Lipids
volume
44
issue
10
pages
897 - 906
publisher
Springer
external identifiers
  • wos:000270895100003
  • pmid:19777283
  • scopus:70350241222
ISSN
0024-4201
DOI
10.1007/s11745-009-3343-1
language
English
LU publication?
yes
id
df3cc049-35d1-46be-a5f3-09acdde44ef2 (old id 1483200)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19777283?dopt=Abstract
date added to LUP
2012-01-19 10:45:02
date last changed
2017-01-01 04:28:25
@article{df3cc049-35d1-46be-a5f3-09acdde44ef2,
  abstract     = {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 &lt; 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 muM 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 muM 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.},
  author       = {Cheng, Yajun and Liu, Fuli and Wu, Jun and Zhang, Yao and Nilsson, Åke and Duan, Rui-Dong},
  issn         = {0024-4201},
  keyword      = {Cholesterol,Hep G2 cells,Rat,Sphingomyelin,Liver,Intestine,Caco-2 cells,Ezetimibe,Acid sphingomyelinase},
  language     = {eng},
  number       = {10},
  pages        = {897--906},
  publisher    = {Springer},
  series       = {Lipids},
  title        = {Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine.},
  url          = {http://dx.doi.org/10.1007/s11745-009-3343-1},
  volume       = {44},
  year         = {2009},
}