Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation

被引:266
作者
Draganov, DI
Stetson, PL
Watson, CE
Billecke, SS
La Du, BN
机构
[1] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA
[3] Mil Med Acad, Lab Expt Toxicol, Sofia 1606, Bulgaria
关键词
D O I
10.1074/jbc.M004543200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:33435 / 33442
页数:8
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