• Beom Jae Lee, Jae Seon Kim, Byung Kyu Kim, Sung Joo Jung, Moon Kyung Joo, Seung Goun Hong, Jang Soo Kim, Ji Hoon Kim, Jong Eun Yeon, Jong-Jae Park, Kwan Soo Byun, Young-Tae Bak, Hwan-Soo Yoo, and Seikwan Oh.
• Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
• J. Gastroenterol. Hepatol. 2010 Jun 1; 25 (6): 1105-10.

BackgroundSphingolipids 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.MethodsThree 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.ResultsMyriocin 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.ConclusionsSPT 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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