Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation
Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation
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DOI：
10.1074/jbc.m004543200
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发表时间：
2000-10-27
影响因子：
4.8
通讯作者：
La Du, BN
中科院分区：
文献类型：
--
作者：
Draganov, DI;Stetson, PL;La Du, BN
二氧酶基因家族至少包含三个成员：PON1，PON2和PON3，相应基因产物的生理作用仍然不确定。直到最近，仅纯化并表征了血清副酶/芳基酶（PON1）。在这里，我们报告了兔血清PON3的纯化，克隆和表征，PON3是一种40 kDa蛋白，与血清的高密度脂蛋白分数相关。与PON1相反，PON3的芳基酯酶非常有限，没有二氧蛋白酶活性，但是迅速水解了诸如他汀类药物前药（例如Lovastatin）之类的内酯，这些差异促进了PON3在纯化过程中与PON3的完全分离。 PON3水解芳香族内酯和5或6个成员的环内酯，带有脂肪族取代基，而不是简单的内酯或具有极性取代基的含量。我们从总兔肝脏RNA克隆了PON3，并在哺乳动物293T/17细胞中表达了PON3，重组PON3具有与从血清纯化的酶相同的明显分子质量和底物特异性。兔血清PON3比兔PON1在保护低密度脂蛋白免受铜诱导的氧化免受的氧化状态更有效，这是第一个鉴定哺乳动物血清中第二个PON酶的报告，并且第一个描述PON3酶活性的酶。
The paraoxonase gene family contains at least three members: PON1, PON2, and PON3, The physiological roles of the corresponding gene products are still uncertain. Until recently, only the serum paraoxonase/arylesterase (PON1) had been purified and characterized. Here we report the purification, cloning, and characterization of rabbit serum PON3, PON3 is a 40-kDa protein associated with the high density lipoprotein fraction of serum. In contrast to PON1, PON3 has very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin), These differences facilitated the complete separation of PON3 from PON1 during purification. PON3 hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. We cloned PON3 from total rabbit liver RNA and expressed it in mammalian 293T/17 cells, The recombinant PON3 has the same apparent molecular mass and substrate specificity as the enzyme purified from serum. Rabbit serum PON3 is more efficient than rabbit PON1 in protecting low density lipoprotein from copper-induced oxidation, This is the first report that identifies a second PON enzyme in mammalian serum and the first to describe an enzymatic activity for PON3.