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Cholesterol Attenuates Cytoprotective Effects of Phosphatidylcholine Against Bile Salts

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Journal Sci Rep
Specialty Science
Date 2017 Mar 24
PMID 28331225
Citations 10
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Abstract

Bile salts have potent detergent properties and damaging effects on cell membranes, leading to liver injury. However, the molecular mechanisms for the protection of hepatocytes against bile salts are not fully understood. In this study, we demonstrated that the cytotoxicity of nine human major bile salts to HepG2 cells and primary human hepatocytes was prevented by phosphatidylcholine (PC). In contrast, cholesterol had no direct cytotoxic effects but suppressed the cytoprotective effects of PC. PC reduced the cell-association of bile salt, which was reversed by cholesterol. Light scattering measurements and gel filtration chromatography revealed that cholesterol within bile salt/PC dispersions decreased mixed micelles but increased vesicles, bile salt simple micelles and monomers. These results suggest that cholesterol attenuates the cytoprotective effects of PC against bile salts by facilitating the formation of bile salt simple micelles and monomers. Therefore, biliary PC and cholesterol may play different roles in the pathogenesis of bile salt-induced liver injury.

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References
1.
CRAWFORD A, Smith A, Hatch V, Oude Elferink R, Borst P, Crawford J . Hepatic secretion of phospholipid vesicles in the mouse critically depends on mdr2 or MDR3 P-glycoprotein expression. Visualization by electron microscopy. J Clin Invest. 1997; 100(10):2562-7. PMC: 508457. DOI: 10.1172/JCI119799. View

2.
Heuman D . Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions. J Lipid Res. 1989; 30(5):719-30. View

3.
Moschetta A, vanBerge-Henegouwen G, Portincasa P, Renooij W, Groen A, van Erpecum K . Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: potential implications for their effects in vivo. J Hepatol. 2001; 34(4):492-9. DOI: 10.1016/s0168-8278(00)00046-5. View

4.
Tougeron D, Fotsing G, Barbu V, Beauchant M . ABCB4/MDR3 gene mutations and cholangiocarcinomas. J Hepatol. 2012; 57(2):467-8. DOI: 10.1016/j.jhep.2012.01.025. View

5.
Lammert F, Wang D, Hillebrandt S, Geier A, Fickert P, Trauner M . Spontaneous cholecysto- and hepatolithiasis in Mdr2-/- mice: a model for low phospholipid-associated cholelithiasis. Hepatology. 2004; 39(1):117-28. DOI: 10.1002/hep.20022. View