Impact of endothelial lipase on cellular lipid composition |
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Authors: | Monika Riederer,Harald Kö feler,Margarete Lechleitner,Michaela Tritscher,Sa&scaron a Frank |
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Affiliation: | 1. Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria;2. Center for Medical Research, Core Facility Mass Spectrometry, Medical University Graz, Graz, Austria |
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Abstract: | Using mass spectrometry (MS), we examined the impact of endothelial lipase (EL) overexpression on the cellular phospholipid (PL) and triglyceride (TG) content of human aortic endothelial cells (HAEC) and of mouse plasma and liver tissue. In HAEC incubated with the major EL substrate, HDL, adenovirus (Ad)-mediated EL overexpression resulted in the generation of various lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) species in cell culture supernatants. While the cellular phosphatidylethanolamine (PE) content remained unaltered, cellular phosphatidylcholine (PC)-, LPC- and TG-contents were significantly increased upon EL overexpression. Importantly, cellular lipid composition was not altered when EL was overexpressed in the absence of HDL. [14C]-LPC accumulated in EL overexpressing, but not LacZ-control cells, incubated with [14C]-PC labeled HDL, indicating EL-mediated LPC supply. Exogenously added [14C]-LPC accumulated in HAEC as well. Its conversion to [14C]-PC was sensitive to a lysophospholipid acyltransferase (LPLAT) inhibitor, thimerosal. Incorporation of [3H]-Choline into cellular PC was 56% lower in EL compared with LacZ cells, indicating decreased endogenous PC synthesis. In mice, adenovirus mediated EL overexpression decreased plasma PC, PE and LPC and increased liver LPC, LPE and TG content. Based on our results, we conclude that EL not only supplies cells with FFA as found previously, but also with HDL-derived LPC and LPE species resulting in increased cellular TG and PC content as well as decreased endogenous PC synthesis. |
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Keywords: | EL, endothelial lipase LPC, lysophosphatidylcholine 16:0 LPC, palmitoyl-lysophosphatidylcholine 18:2 LPC, linoleoyl-LPC 20:4 LPC, arachidonoyl-LPC 18:1 LPC, oleoyl-LPC HAEC, human aortic endothelial cells AA, arachidonic acid PL, phospholipids LysoPL, lysophospholipids HDL, high-density lipoprotein ATGL, adipose triglyceride lipase DGAT, diacylglycerol acyltransferase CT, CTP:phosphocholine cytidylyltransferase ET, CTP:phosphoethanolamine cytidylyltransferase LPLATs, lysophospholipid acyltransferases BSA, bovine serum albumin FCS, fetal calf serum MS, mass spectrometry |
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