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

Beomjae 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, Seikwan Oh

Research output: Contribution to journalArticle

3 Citations (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.

Original languageEnglish
Pages (from-to)1105-1110
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume25
Issue number6
DOIs
Publication statusPublished - 2010 Jan 1

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Sphingolipids
Gallstones
Serine C-Palmitoyltransferase
Inbred C57BL Mouse
Ceramides
Cholesterol
Bile
Diet
Gallbladder
Serum
Biosynthetic Pathways
Lipoproteins
thermozymocidin
Signal Transduction
Western Blotting
Phosphates
High Pressure Liquid Chromatography
Phosphorylation
Cell Membrane
Proteins

Keywords

  • Cholesterol gallstone
  • Myriocin
  • P38
  • Sphingolipid

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice. / Lee, Beomjae; Kim, Jae Seon; Kim, Byung Kyu; Jung, Sung Joo; Joo, Moon Kyung; Hong, Seung Goun; Kim, Jang Soo; Kim, Ji Hoon; Yeon, Jong Eun; Park, Jong Jae; Byun, Kwan Soo; Bak, Young-Tae; Yoo, Hwan Soo; Oh, Seikwan.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 25, No. 6, 01.01.2010, p. 1105-1110.

Research output: Contribution to journalArticle

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AU - Kim, Jae Seon

AU - Kim, Byung Kyu

AU - Jung, Sung Joo

AU - Joo, Moon Kyung

AU - Hong, Seung Goun

AU - Kim, Jang Soo

AU - Kim, Ji Hoon

AU - Yeon, Jong Eun

AU - Park, Jong Jae

AU - Byun, Kwan Soo

AU - Bak, Young-Tae

AU - Yoo, Hwan Soo

AU - Oh, Seikwan

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N2 - 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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