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

Title
Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice
Authors
Lee B.J.Kim J.S.Kim B.K.Jung S.J.Joo M.K.Hong S.G.Kim J.H.Yeon J.E.Park J.-J.Byun K.S.Bak Y.-T.Yoo H.-S.Oh S.
Ewha Authors
오세관
SCOPUS Author ID
오세관scopus
Issue Date
2010
Journal Title
Journal of Gastroenterology and Hepatology
ISSN
0815-9319JCR Link
Citation
vol. 25, no. 6, pp. 1105 - 1110
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
DOI
10.1111/j.1440-1746.2010.06246.x
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의학전문대학원 > 의학과 > Journal papers
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