title: Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation.
abstract: The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.
authors.affiliation: Division of Cardiovascular Research, University of Manchester, Oxford Road, Manchester M13 9WL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hine
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Mike
authors.initials: M
authors.lastname: Mackness
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry*; D043303:Aryldialkylphosphatase / Q000737:chemistry*; D004951:Esterification; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human