Mevalonate inhibits acid sphingomyelinase activity, increases sphingomyelin levels and inhibits cell proliferation of HepG2 and Caco-2 cells

Lipids in Health and Disease

Rui-Dong Duan²  Shu-Chang Xu¹  Ying Chen¹ 

[1] Gastroenterology, Tongji Hospital, Tongji University Medical School, Shanghai, 200065, China;Gastroenterology and Nutrition Laboratory, Department of Clinical Sciences, University of Lund, Lund, S 22184, Sweden

关键词: Caco-2;    HepG2;    Phosphatidylcholine;    Cell proliferation;    Acid sphingomyelinase;    Cholesterol;    Sphingomyelin;    Mevalonate;   

Others  :  1231340
DOI  :  10.1186/s12944-015-0137-8

 received in 2015-03-30, accepted in 2015-10-15,  发布年份 2015

【 摘 要 】

Background

Sphingomyelin (SM) and cholesterol are two types of lipid closely related biophysically. Treating the cells with exogenous sphingomyelinase (SMase) induces trafficking of cholesterol from membrane to intracellular pools and inhibition of cholesterol synthesis. In the present work, we address a question whether increased cholesterol synthesis affects hydrolysis of SM by endogenous SMases.

Methods

Both HepG2 and Caco-2 cells were incubated with mevalonate. The SMase activity was determined and its mRNA examined by qPCR. The cellular levels of cholesterol, SM, and phosphatidylcholine (PC) were determined and cell proliferation rate assayed.

Results

We found that mevalonate dose-dependently decreased acid but not neutral SMase activity in both HepG2 and Caco-2 cells with HepG2 cells being more sensitive to mevalonate. Kinetic examination in HepG2 cells revealed that acid SMase activity was increasing with cell proliferation, and such an increase was reversed by mevalonate treatment. Acid SMase mRNA was not significantly decreased and Western blot showed signs of proteolysis of acid SMase by mevalonate. After mevalonate treatment, the levels of cholesterol were significantly increased associated with increases in SM and PC. The cell growth was retarded by mevalonate and the effect was more obvious in HepG2 cells than in Caco-2 cells.

Conclusion

Mevalonate can trigger a mechanism to enhance SM levels by inhibition of acid SMase. The effect may ensure the coordinate changes of SM and cholesterol in the cells. Mevalonate also affects cell growth with mechanism required further characterization.

【 授权许可】

   
2015 Chen et al.

【 图 表 】

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