Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein
Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein
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DOI：
10.1074/jbc.m105660200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Reddy, ST
中科院分区：
文献类型：
--
作者：
Ng, CJ;Wadleigh, DJ;Reddy, ST
含载脂蛋白B的脂蛋白和细胞膜脂质的氧化被认为在脂肪条纹病变的发展中起着不可或缺的作用，脂肪条纹病变是动脉粥样硬化形成的初始步骤。我们先前已经表明，两种抗氧化剂样酶，对氧磷酶（PON）-1和PON 3，是能够防止低密度脂蛋白（LDL）氧化修饰的高密度脂蛋白相关蛋白（Reddy，S. T.，Wadleigh，D. J.，Grijalva，V.，Ng，C.，Hama，S.，Gango-padhyay，A.，Shih，D. M.，Lusis，A. J.，Navab，M.，和Fogelman，A. M. 04 The Dog of the Woman（2001）Thromb.花瓶21，542-547）。在本研究中，我们证明PON 2（i）与高密度脂蛋白无关;（ii）具有抗氧化特性;（iii）防止LDL脂质过氧化，逆转轻度氧化LDL（MM-LDL）的氧化，并抑制MM-LDL诱导单核细胞趋化性的能力。PON 2蛋白使用四环素诱导（“Tet-On”）系统在HeLa细胞中过表达，并在荧光测定中测量其抗氧化能力。过表达PON 2的细胞在用过氧化氢或氧化磷脂处理后显示出显著更少的细胞内氧化应激。此外，过表达PON 2的细胞在氧化和修饰LDL方面也不那么有效，事实上，能够逆转预先形成的MM-LDL的作用。我们的研究结果表明，PON 2具有类似的PON 1和PON 3的抗氧化性能。然而，与PON 1和PON 3相反，PON 2可以在细胞水平上发挥其抗氧化功能，加入保护细胞免受氧化应激的细胞内抗氧化酶的宿主。
The oxidation of apolipoprotein B-containing lipoproteins and cell membrane lipids is believed to play an integral role in the development of fatty streak lesions, an initial step in atherogenesis. We have previously shown that two antioxidant-like enzymes, paraoxonase (PON)-1 and PON3, are high density lipoprotein-associated proteins capable of preventing the oxidative modification of low density lipoprotein (LDL) (Reddy, S. T., Wadleigh, D. J., Grijalva, V., Ng, C., Hama, S., Gango-padhyay, A., Shih, D. M., Lusis, A. J., Navab, M., and Fogelman, A. M. (2001) Arterioscler. Thromb. Vase. Biol. 21, 542-547). In the present study, we demonstrate that PON2 (i) is not associated with high density lipoprotein; (ii) has antioxidant properties; and (iii) prevents LDL lipid peroxidation, reverses the oxidation of mildly oxidized LDL (MM-LDL), and inhibits the ability of MM-LDL to induce monocyte chemotaxis. The PON2 protein was overexpressed in HeLa cells using the tetracycline-inducible ("Tet-On") system, and its antioxidant capacity was measured in a fluorometric assay. Cells that overexpressed PON2 showed significantly less intracellular oxidative stress following treatment with hydrogen peroxide or oxidized phospholipid. Moreover, cells that overexpressed PON2 were also less effective in oxidizing and modifying LDL and, in fact, were able to reverse the effects of preformed MM-LDL. Our results suggest that PON2 possesses antioxidant properties similar to those of PON1 and PON3. However, in contrast to PON1 and PON3, PON2 may exert its antioxidant functions at the cellular level, joining the host of intracellular antioxidant enzymes that protect cells from oxidative stress.