Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis

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作者：

Shih,DM，Gu,L，Xia,YR，Navab,M，Li,WF，Hama,S，Castellani,LW，Furlong,CE，Costa,LG，Fogelman,AM

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摘要：

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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关键词：

Atherosclerosis Chlorpyrifos Esterases Insecticides Organothiophosphate 动脉粥样硬化毒死蜱酯酶类杀虫药有机硫磷