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Abstract

Serum paraoxonase (PON1) is an esterase that is associated with high-density lipoproteins (HDLs) in the plasma; it is involved in the detoxification of organophosphate insecticides such as parathion and chlorpyrifos. PON1 may also confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids present in oxidized low-density lipoproteins (LDLs). To study the role of PON1 in vivo, we created PON1-knockout mice by gene targeting. Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from PON1-deficient mice were unable to prevent LDL oxidation in a co-cultured cell model of the artery wall, and both HDLs and LDLs isolated from PON1-knockout mice were more susceptible to oxidation by co-cultured cells than the lipoproteins from wild-type littermates. When fed on a high-fat, high-cholesterol diet, PON1-null mice were more susceptible to atherosclerosis than their wild-type littermates.

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PubMed ID:: 9685159

DOI:: 10.1038/28406

ScienceOpen disciplines: Chemistry

Keywords: Animals,Aorta,pathology,Arteriosclerosis,etiology,Aryldialkylphosphatase,Cells, Cultured,Chlorpyrifos,analogs & derivatives,toxicity,Cholinesterase Inhibitors,Coculture Techniques,Diet, Atherogenic,Esterases,blood,deficiency,genetics,physiology,Female,Humans,Inactivation, Metabolic,Insecticides,Lipid Peroxides,metabolism,Lipoproteins, HDL,Lipoproteins, LDL,Male,Mice,Mice, Inbred C57BL,Mice, Knockout,Oxidation-Reduction,Restriction Mapping,Risk Factors

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ScienceOpen disciplines: Chemistry

Keywords: Animals, Aorta, pathology, Arteriosclerosis, etiology, Aryldialkylphosphatase, Cells, Cultured, Chlorpyrifos, analogs & derivatives, toxicity, Cholinesterase Inhibitors, Coculture Techniques, Diet, Atherogenic, Esterases, blood, deficiency, genetics, physiology, Female, Humans, Inactivation, Metabolic, Insecticides, Lipid Peroxides, metabolism, Lipoproteins, HDL, Lipoproteins, LDL, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxidation-Reduction, Restriction Mapping, Risk Factors

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