Lipoprotein lipase mediated uptake of non-degradable ether analogues of phosphatidylcholine and cholesteryl ester by cultured cells.
Lipoprotein lipase mediated transfer of cholesteryl ester and its ether analog, cholesteryl linoleyl ether, from unilamellar liposomes, prepared from a nonhydrolyzable ether analog of 1,2-diacyl-sn-glycero-3-phosphocholine (PC), 1,2-dioleyl ether-sn-glycero-3-phosphocholine (DOEPC), was studied in various cells in culture. It was found that lipoprotein lipase enhanced the uptake of cholesteryl linoleyl ether and of DOEPC. These findings provided a definitive proof that hydrolysis of liposomal PC is not needed for the lipoprotein lipase catalyzed transfer of cholesteryl linoleyl ether and cholesteryl ester to cells. The lipids transferred by lipoprotein lipase to cells were localized in three compartments, trypsin-releasable, resistant and metabolic; the latter was a chloroquine-sensitive pool as evidenced by inhibition of cholesteryl ester hydrolysis. Labeled PC and, to a lesser extent DOEPC, in the trypsin-releasable pool was able to return to the medium, while cholesteryl linoleyl ether and cholesteryl ester required cholesteryl ester transfer protein for release. The transfer of cholesteryl linoleyl ether and cholesteryl ester into a trypsin-resistant compartment did not require metabolic energy and occurred also in formaldehyde-fixed cells. Metabolic energy was needed for the translocation of cholesteryl linoleyl ether and cholesteryl ester into the lysosomal compartment, presumably by a process of endocytosis. The physiological relevance of the present findings is that as intravascular hydrolysis of triacylglycerol-rich lipoproteins is mediated by lipoprotein lipase attached to endothelial cells, the latter can provide a very extensive surface for removal and metabolism of phospholipids and cholesteryl ester by a mechanism mediated by lipoprotein lipase.
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000378:metabolism
D002788:Cholesterol Esters; D003486:Cyanides; D008081:Liposomes; D010713:Phosphatidylcholines; D003847:Deoxyglucose; D008071:Lipoprotein Lipase