| Effects of sphingolipid synthesis inhibition on cholesterol gallstone formation in C57BL/6J mice. | |
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MedLine Citation:
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PMID: 20594226 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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; Seikwan Oh |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of gastroenterology and hepatology Volume: 25 ISSN: 1440-1746 ISO Abbreviation: J. Gastroenterol. Hepatol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-10-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607909 Medline TA: J Gastroenterol Hepatol Country: Australia |
Other Details:
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Languages: eng Pagination: 1105-10 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism Blotting, Western Ceramides / metabolism Cholesterol / metabolism* Chromatography, High Pressure Liquid Disease Models, Animal Extracellular Signal-Regulated MAP Kinases / biosynthesis Fatty Acids, Monounsaturated / administration & dosage* Gallbladder / metabolism Gallstones / chemically induced, drug therapy*, metabolism Immunosuppressive Agents / administration & dosage* JNK Mitogen-Activated Protein Kinases / biosynthesis Male Mice Mice, Inbred C57BL Sphingolipids / antagonists & inhibitors*, biosynthesis Treatment Outcome Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Ceramides; 0/Fatty Acids, Monounsaturated; 0/Immunosuppressive Agents; 0/Sphingolipids; 0/Triglycerides; 35891-70-4/thermozymocidin; 57-88-5/Cholesterol; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
Comment In:
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J Gastroenterol Hepatol. 2010 Jun;25(6):1020-3
[PMID:
20594212
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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