Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts

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 ma...

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Autores principales:	Yoshito Ikeda, Shin-ya Morita, Tomohiro Terada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a6b12d6dcd841089fa8d32655972a4b
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spelling	oai:doaj.org-article:0a6b12d6dcd841089fa8d32655972a4b2021-12-02T12:32:33ZCholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts10.1038/s41598-017-00476-22045-2322https://doaj.org/article/0a6b12d6dcd841089fa8d32655972a4b2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00476-2https://doaj.org/toc/2045-2322Abstract 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.Yoshito IkedaShin-ya MoritaTomohiro TeradaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshito Ikeda Shin-ya Morita Tomohiro Terada Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
description	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.
format	article
author	Yoshito Ikeda Shin-ya Morita Tomohiro Terada
author_facet	Yoshito Ikeda Shin-ya Morita Tomohiro Terada
author_sort	Yoshito Ikeda
title	Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
title_short	Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
title_full	Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
title_fullStr	Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
title_full_unstemmed	Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
title_sort	cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0a6b12d6dcd841089fa8d32655972a4b
work_keys_str_mv	AT yoshitoikeda cholesterolattenuatescytoprotectiveeffectsofphosphatidylcholineagainstbilesalts AT shinyamorita cholesterolattenuatescytoprotectiveeffectsofphosphatidylcholineagainstbilesalts AT tomohiroterada cholesterolattenuatescytoprotectiveeffectsofphosphatidylcholineagainstbilesalts
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Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts

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