Lipoprotein desialylation simultaneously enhances the cell cholesterol uptake and impairs the reverse cholesterol transport system: in vitro evidences utilizing neuraminidase-treated lipoproteins and mouse peritoneal macrophages.
Desialylation of low density lipoprotein (LDL) brings about accumulation of cholesterol in cultured cells. The influence of the neuraminidase-treated lipoprotein (LP) on the reverse cholesterol transport system was investigated in vitro utilizing very low density lipoprotein (VLDL), LDL, total high density lipoprotein (HDL) and its subfractions, HDL2 and HDL3, isolated from healthy donor plasma and mouse peritoneal macrophages. It was found that LP desialylation significantly: (1) decreased the capacity of total HDL and of HDL2, but not of HDL3, to efflux cellular cholesterol; (2) lowered the cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT) without modifying the intrinsic LCAT activity of HDL; (3) increased the cholesteryl ester transfer from HDL to apo B-containing LP mediated by cholesteryl ester transfer protein (CETP); (4) enhanced the uptake by macrophages of cholesterol from HDL and LDL, although the amount of cholesterol taken up by the cells was much greater from the desialylated LDL than from desialylated HDL. Taken together, these in vitro evidences indicate that, in addition to enhancing the cell cholesterol LP uptake, desialylation may contribute to the premature development of atherosclerosis by impairing the reverse cholesterol transport system.
Harada
L M
LM
Lipids Laboratory (LIM-10), University of São Paulo Medical School, Brazil.
Carvalho
M D
MD
Passarelli
M
M
Quintão
E C
EC
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins; D012794:Sialic Acids; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D009439:Neuraminidase