Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection?

Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection?
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DOI:
10.1007/s11064-013-1085-1
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发表时间:
2013-09
影响因子:
4.4
通讯作者:
Furlong, Clement E.
Furlong, Clement E.
中科院分区:
医学3区
文献类型:
--
作者:
Costa, Lucio G.;Tait, Leah;de Laat, Rian;Dao, Khoi;Giordano, Gennaro;Pellacani, Claudia;Cole, Toby B.;Furlong, Clement E.

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槲皮素是一种常见的黄酮类多酚类化合物,已被证明在体外和体内具有神经保护作用。虽然Quercetin具有抗氧化特性,但有人认为,神经保护可能归因于它诱导细胞自身防御机制的能力。这项研究调查了栎素是否可以增加脑细胞中表达的线粒体酶对氧磷酶2(PON2)的水平,这种酶已被证明具有强大的抗氧化特性。在小鼠纹状体星形胶质细胞中,PON2蛋白、mRNA和乳糖酶活性最高。栎素可能通过激活JNK/AP-1途径增加PON_2水平。槲皮素诱导的PON_2水平升高导致氧化应激降低,两种氧化剂引起的毒性也随之降低。在PON2基因敲除小鼠的细胞中,槲皮素的神经保护作用显著减弱。这些发现表明,槲皮素诱导PON_2是这种多酚发挥神经保护作用的重要机制。
Quercetin is a common flavonoid polyphenol which has been shown to exert neuroprotective actions in vitro and in vivo. Though quercetin has antioxidant properties, it has been suggested that neuroprotection may be ascribed to its ability of inducing the cell’s own defense mechanisms. The present study investigated whether quercetin could increase the levels of paraoxonase 2 (PON2), a mitochondrial enzyme expressed in brain cells, which has been shown to have potent antioxidant properties. PON2 protein, mRNA, and lactonase activity were highest in mouse striatal astrocytes. Quercetin increased PON2 levels, possibly by activating the JNK/AP-1 pathway. The increased PON2 levels induced by quercetin resulted in decreased oxidative stress and ensuing toxicity induced by two oxidants. The neuroprotective effect of quercetin was significantly diminished in cells from PON2 knockout mice. These findings suggest that induction of PON2 by quercetin represents an important mechanism by which this polyphenol may exert its neuroprotective action.
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