Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE
Liver is the sole organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or bile acids. High density lipoprotein (HDL)-derived cholesterol is the major source of biliary sterols and represents a mechanism for the removal of cholesterol from peripheral...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-11-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520350598 |
| _version_ | 1818727884799344640 |
|---|---|
| author | Quan Yuan Jinghua Bie Jing Wang Siddhartha S. Ghosh Shobha Ghosh |
| author_facet | Quan Yuan Jinghua Bie Jing Wang Siddhartha S. Ghosh Shobha Ghosh |
| author_sort | Quan Yuan |
| collection | DOAJ |
| description | Liver is the sole organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or bile acids. High density lipoprotein (HDL)-derived cholesterol is the major source of biliary sterols and represents a mechanism for the removal of cholesterol from peripheral tissues including artery wall-associated macrophage foam cells. Via selective uptake through scavenger receptor BI (SR-BI), HDL-cholesterol is thought to be directly secreted into bile, and HDL cholesteryl esters (HDL-CEs) enter the hepatic metabolic pool and need to be hydrolyzed prior to conversion to bile acids. However, the identity of hepatic CE hydrolase (CEH) as well as the role of SR-BI in bile acid synthesis remains elusive. In this study we examined the role of human hepatic CEH (CES1) in facilitating hydrolysis of SR-BI-delivered HDL-CEs. Over-expression of CEH led to increased hydrolysis of HDL-[3H]CE in primary hepatocytes and SR-BI expression was required for this process. Intracellular CEH associated with BODIPY-CE delivered by selective uptake via SR-BI. CEH and SR-BI expression enhanced the movement of [3H]label from HDL-[3H]CE to bile acids in vitro and in vivo. Taken together, these studies demonstrate that SR-BI-delivered HDL-CEs are hydrolyzed by hepatic CEH and utilized for bile acid synthesis. |
| first_indexed | 2024-12-17T22:21:12Z |
| format | Article |
| id | doaj.art-4e4c52eee58e47ef8236e50d3283b9fa |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:21:12Z |
| publishDate | 2013-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4e4c52eee58e47ef8236e50d3283b9fa2022-12-21T21:30:28ZengElsevierJournal of Lipid Research0022-22752013-11-01541130783084Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CEQuan Yuan0Jinghua Bie1Jing Wang2Siddhartha S. Ghosh3Shobha Ghosh4Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050To whom correspondence should be addressed; Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0050Liver is the sole organ responsible for the final elimination of cholesterol from the body either as biliary cholesterol or bile acids. High density lipoprotein (HDL)-derived cholesterol is the major source of biliary sterols and represents a mechanism for the removal of cholesterol from peripheral tissues including artery wall-associated macrophage foam cells. Via selective uptake through scavenger receptor BI (SR-BI), HDL-cholesterol is thought to be directly secreted into bile, and HDL cholesteryl esters (HDL-CEs) enter the hepatic metabolic pool and need to be hydrolyzed prior to conversion to bile acids. However, the identity of hepatic CE hydrolase (CEH) as well as the role of SR-BI in bile acid synthesis remains elusive. In this study we examined the role of human hepatic CEH (CES1) in facilitating hydrolysis of SR-BI-delivered HDL-CEs. Over-expression of CEH led to increased hydrolysis of HDL-[3H]CE in primary hepatocytes and SR-BI expression was required for this process. Intracellular CEH associated with BODIPY-CE delivered by selective uptake via SR-BI. CEH and SR-BI expression enhanced the movement of [3H]label from HDL-[3H]CE to bile acids in vitro and in vivo. Taken together, these studies demonstrate that SR-BI-delivered HDL-CEs are hydrolyzed by hepatic CEH and utilized for bile acid synthesis.http://www.sciencedirect.com/science/article/pii/S0022227520350598HDL-cholesteryl esterbile acid synthesischolesteryl ester |
| spellingShingle | Quan Yuan Jinghua Bie Jing Wang Siddhartha S. Ghosh Shobha Ghosh Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE Journal of Lipid Research HDL-cholesteryl ester bile acid synthesis cholesteryl ester |
| title | Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE |
| title_full | Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE |
| title_fullStr | Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE |
| title_full_unstemmed | Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE |
| title_short | Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE |
| title_sort | cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor bi for hydrolysis of hdl ce |
| topic | HDL-cholesteryl ester bile acid synthesis cholesteryl ester |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520350598 |
| work_keys_str_mv | AT quanyuan cooperationbetweenhepaticcholesterylesterhydrolaseandscavengerreceptorbiforhydrolysisofhdlce AT jinghuabie cooperationbetweenhepaticcholesterylesterhydrolaseandscavengerreceptorbiforhydrolysisofhdlce AT jingwang cooperationbetweenhepaticcholesterylesterhydrolaseandscavengerreceptorbiforhydrolysisofhdlce AT siddharthasghosh cooperationbetweenhepaticcholesterylesterhydrolaseandscavengerreceptorbiforhydrolysisofhdlce AT shobhaghosh cooperationbetweenhepaticcholesterylesterhydrolaseandscavengerreceptorbiforhydrolysisofhdlce |