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Hepatic uptake and metabolism of phosphatidylcholine associated with high density lipoproteins
Authors:Julie C. Robichaud  Jelske N. van der Veen  Zemin Yao  Bernardo Trigatti  Dennis E. Vance
Affiliation:1. Group on the Molecular and Cell Biology of Lipids and the Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5;3. Atherothrombosis Research Group and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
Abstract:

Background

Phosphatidylcholine (PC) is the predominant phospholipid associated with high density lipoproteins (HDL). Although the hepatic uptake of cholesteryl esters from HDL is well characterized, much less is known about the fate of PC associated with HDL. Thus, we investigated the uptake and subsequent metabolism of HDL-PC in primary mouse hepatocytes.

Methods and results

The absence of scavenger receptor-BI resulted in a 30% decrease in cellular incorporation of [3H]PC whereas [3H]cholesteryl ether uptake was almost completely abolished. Although endocytosis is not involved in the uptake of cholesteryl esters from HDL, we demonstrate that HDL internalization accounts for 40% of HDL-PC uptake. Extracellular remodeling of HDL by secretory phospholipase A2 significantly enhances HDL lipid uptake. HDL-PC taken up by hepatocytes is partially converted to triacylglycerols via PC-phospholipase C-mediated hydrolysis of PC and incorporation of diacylglycerol into triacylglcyerol. The formation of triacylglcerol is independent of scavenger receptor-BI and occurs in extralysosomal compartments.

Conclusions and general significance

These findings indicate that HDL-associated PC is incorporated into primary hepatocytes via a pathway that differs significantly from that of HDL-cholesteryl ester, and shows that HDL-PC is more than a framework molecule, as evidenced by its partial conversion to hepatic triacylglycerol.
Keywords:ATK, arachidonyl trifluoromethyl ketone   CE, cholesteryl ester   CEt, cholesteryl ether   CETP, cholesterol ester transfer protein   DGAT, diacylglycerol acyltransferase   DMEM, Dulbecco's modified Eagle's medium   HDL, high density lipoprotein   HL, hepatic lipase   LCAT, lecithin:cholesterol acyltransferase   LDL, low density lipoprotein   LDLr, low density lipoprotein receptor   LPL, lipoprotein lipase   PBS, phosphate buffered saline   PC, phosphatidylcholine   PLA2, phospholipase A2   PLC, phospholipase C   SR-BI, scavenger receptor class B type I   TG, triacylglycerol
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