Shih_1998_Nature_394_284

Reference

Title : Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis - Shih_1998_Nature_394_284
Author(s) : Shih DM , Gu L , Xia YR , Navab M , Li WF , Hama S , Castellani LW , Furlong CE , Costa LG , Fogelman AM , Lusis AJ
Ref : Nature , 394 :284 , 1998
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.
ESTHER : Shih_1998_Nature_394_284
PubMedSearch : Shih_1998_Nature_394_284
PubMedID: 9685159

Related information

Inhibitor ChlorpyrifosParathion

Citations formats

Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ (1998)
Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis
Nature 394 :284

Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ (1998)
Nature 394 :284

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    [paper] => Shih_1998_Nature_394_284
    [author] => Shih DM || Gu L || Xia YR || Navab M || Li WF || Hama S || Castellani LW || Furlong CE || Costa LG || Fogelman AM || Lusis AJ
    [year] => 1998
    [title] => Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis
    [journal] => Nature
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    [abstract] => Shih_1998_Nature_394_284
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            [content] => 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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