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Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice

Authors
Lee, Beom JaeKim, Jae SeonKim, Byung KyuJung, Sung JooJoo, Moon KyungHong, Seung GounKim, Jang SooKim, Ji HoonYeon, Jong EunPark, Jong-JaeByun, Kwan SooBak, Young-TaeYoo, Hwan-SooOh, Seikwan
Issue Date
Jun-2010
Publisher
Blackwell Publishing Inc.
Keywords
cholesterol gallstone; myriocin; p38; sphingolipid
Citation
Journal of Gastroenterology and Hepatology, v.25, no.6, pp.1105 - 1110
Indexed
SCIE
SCOPUS
Journal Title
Journal of Gastroenterology and Hepatology
Volume
25
Number
6
Start Page
1105
End Page
1110
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/14828
DOI
10.1111/j.1440-1746.2010.06246.x
ISSN
0815-9319
Abstract
Background: Sphingolipids play a very important role in cell membrane formation, signal transduction and plasma lipoprotein metabolism. The first rate-limiting step in the sphingolipid biosynthetic pathway is catalyzed by serine palmitoyltransferase (SPT), and myriocin is a potent and specific inhibitor of SPT. We investigated the impact of SPT inhibition on cholesterol gallstone formation in C57BL/6J mice. Methods: Three groups of eight-week-old C57BL/6J mice were utilized. Each group consisted of 20 mice; group A, B, and C were fed normal chow, lithogenic diet with phosphate buffered saline, and lithogenic diet with myriocin (0.3 mg/kg), respectively, for 6 weeks. The ceramide levels in both serum and bile were assessed by high performance liquid chromatography analysis. Protein expression of ERK, JNK and p38 in the extracted gallbladder were determined by Western-blot analysis. Results: Myriocin treatment caused a significant decrease in the rate of cholesterol gallstone formation. The lithogenic diet mice (group B) showed the highest ceramide activities in both the serum and bile among all the tested groups and there was significant suppression of the ceramide levels in both the serum and bile of the myriocin-treated mice (group C, p < 0.05). Phosphorylation of p38 in the gallbladder was increased in the lithogenic-diet mice and the expression of phosphorylated p38 was significantly suppressed in the myriocin treated mice. Conclusions: SPT inhibition by myriocin suppressed gallstone formation and the levels of ceramide in both the serum and bile. p38 in the cellular signaling pathways might be associated with cholesterol gallstone formation.
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Kim, Jae Seon
Guro Hospital (Department of Gastroenterology and Hepatology, Guro Hospital)
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