Metabolism of Oxidized Low Density Lipoprotein by Lecithin-Colesterol Acyltransferse

The possible involvement of lecithincholesterol acyltransferase (LCAT) in The metabolism ofoxidized phosphatidylcholine (PC) in plasma was investigated. A variety of oxidized产品areformed from PC following oxidation of low density lipoproteins (LDL). A significant increase in LDLoxidation level in patients with familial LCAT deficiency (FLD) has been previously demonstrated bya sensitive sandwich ELISA for oxidized LDL using the monoclonal antibody DLH3 which recognizesoxidized products of PC. In the present study，我们发现LCAT产品various metabolites from oxidized PC and that oxidized PC molecules inLDL particles serve as substrates. When the neutral lipid fraction was separated by TLC after theincubation of oxidized 1-palmitoyl-2-[1i D114 D1C] linoleoyl PC with human plasma，a number of radioactive bands for cholesteryl ester.这些产品不是formed from native 1-palmitoyl-2-[1- i D114 - i D1C] linoleoyl PC. Plasma from FLD patie…More nts also failed to form the additional products from oxidized PC. the addition ofdithio-bis(nitrobenzoate) (DTNB), an LCAT inhibitoror the inactivation of LCAT activity by treating the plasma at 56c for 30 min abolished thegeneration of这些产品from oxidized PC. The activity was recovered in The high densitylipoprotein (HDL) fraction but in the LDL fraction separated from正常plasma. When1-palmitoyl-2-[1- oxononanoyl) PC和1-stearoyl-2-[1- oxovaleroyl)PC, PC oxidation products that contain short chain aldehydes, were incubated with human plasmaradioactive products in the neutral lipid fraction were observed on TLC. LDL containing oxidized PCwas measured by sandwich ELISA使用an anti-apolipoprotein B antibody and DLH3.The reconstitutedoxidized PC-LDL particles found to have lost their ability to bind DLH3 upon incubation withhdl,while the reactivity of the reconstituted oxidized PC-LDL remained unchanged in the presence ofDTNB. LCAT is capable of metabolizing a variety of oxidized products ofPC and preventing the accumulation of oxidized PC in circulating LDL particles. Less

The possible involvement of lecithin-cholesterol acyltransferase (LCAT) in the metabolism of oxidized phosphatidylcholine (PC) in plasma was investigated. A variety of oxidized products are formed from PC following oxidation of low density lipoproteins (LDL). A significant increase in LDL oxidation levels in patients with familial LCAT deficiency (FLD) has been previously demonstrated by a sensitive sandwich ELISA for oxidized LDL using the monoclonal antibody DLH3 which recognizes oxidized products of PC. In the present study, we found that LCAT produces various metabolites from oxidized PC and that oxidized PC molecules in LDL particles serve as substrates. When the neutral lipid fraction was separated by TLC after the incubation of oxidized 1-palmitoyl-2-[1 ィイD114ィエD1C] linoleoyl PC with human plasma, a number of radioactive bands were formed in addition to cholesteryl ester. These products were not formed from native 1-palmitoyl-2-[1-ィイD114ィエD1C] linoleoyl PC. Plasma from FLD patie … More nts also failed to form the additional products from oxidized PC. The addition of dithio-bis(nitrobenzoate) (DTNB), an LCAT inhibitor, or the inactivation of LCAT activity by treating the plasma at 56 C for 30 min abolished the generation of these products from oxidized PC. The activity was recovered in the high density lipoprotein (HDL) fraction but not in the LDL fraction separated from normal plasma. When 1-palmitoyl-2-[1-ィイD114ィエD1C] (9-oxononanoyl) PC and 1-stearoyl-2-[1-ィイD114ィエD1C] (5-oxovaleroyl) PC, PC oxidation products that contain short chain aldehydes, were incubated with human plasma, radioactive products in the neutral lipid fraction were observed on TLC. LDL containing oxidized PC was measured by sandwich ELISA using an anti-apolipoprotein B antibody and DLH3.The reconstituted oxidized PC-LDL particles were found to have lost their ability to bind DLH3 upon incubation with HDL, while the reactivity of the reconstituted oxidized PC-LDL remained unchanged in the presence of DTNB. These results suggest that LCAT is capable of metabolizing a variety of oxidized products of PC and preventing the accumulation of oxidized PC in circulating LDL particles. Less