Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine.
(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:
https://lup.lub.lu.se/record/1483200
- author
- Cheng, Yajun LU ; Liu, Fuli LU ; Wu, Jun LU ; Zhang, Yao LU ; Nilsson, Åke LU and Duan, Rui-Dong LU
- organization
- publishing date
- 2009
- 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
- 2016-04-01 11:43:03
- date last changed
- 2024-01-07 17:50:23
@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 < 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}}, keywords = {{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}}, doi = {{10.1007/s11745-009-3343-1}}, volume = {{44}}, year = {{2009}}, }