Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection
Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection
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DOI：
10.1016/j.neuro.2013.08.011
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发表时间：
2014-07-01
期刊：
影响因子：
3.4
通讯作者：
Furlong, Clement E.
中科院分区：
文献类型：
--
作者：
Costa, Lucio G.;de Laat, Rian;Furlong, Clement E.
对氧磷酶2 （PON2）是一个基因家族的成员，该基因家族还包括研究较多的PON1和PON3。PON2在三种pon中是独特的，因为它在脑组织中表达。PON2是一种内酯酶，具有抗氧化和抗炎的特性。PON2水平在多巴胺能区（如纹状体）中最高，在星形胶质细胞中高于神经元，在雌性小鼠的大脑和外周组织中高于雄性小鼠。在亚细胞水平，PON2主要定位于线粒体，在那里它清除超氧化物。缺乏PON2（如PON2（-/-）小鼠）或PON2水平较低（如雄性小鼠与雌性相比）会增加对氧化应激诱导的毒性的易感性。雌二醇增加PON2在体内和体外的表达，并提供抗氧化应激的神经保护。这种神经保护在PON2（-/-）小鼠的中枢神经系统细胞中不存在。多酚槲皮素也有类似的结果。PON2具有细胞定位和抗氧化、抗炎作用，可能是参与神经保护的相关酶，可能是神经保护策略的新靶点。它在男性和女性中的差异表达可以解释各种疾病发病率的性别差异，包括神经发育、神经和神经退行性疾病。(C) 2013爱思唯尔公司版权所有。
Paraoxonase 2 (PON2) is a member of a gene family which also includes the more studied PON1, as well as PON3. PON2 is unique among the three PONs, as it is expressed in brain tissue. PON2 is a lactonase and displays anti-oxidant and anti-inflammatory properties. PON2 levels are highest in dopaminergic regions (e.g. striatum), are higher in astrocytes than in neurons, and are higher in brain and peripheral tissues of female mice than male mice. At the sub-cellular level, PON2 localizes primarily in mitochondria, where it scavenges superoxides. Lack of PON2 (as in PON2(-/-) mice), or lower levels of PON2 (as in male mice compared to females) increases susceptibility to oxidative stress-induced toxicity. Estradiol increases PON2 expression in vitro and in vivo, and provides neuroprotection against oxidative stress. Such neuroprotection is not present in CNS cells from PON2(-/-) mice. Similar results are also found with the polyphenol quercetin. PON2, given its cellular localization and antioxidant and anti-inflammatory actions, may represent a relevant enzyme involved in neuroprotection, and may represent a novel target for neuroprotective strategies. Its differential expression in males and females may explain gender differences in the incidence of various diseases, including neurodevelopmental, neurological, and neurodegenerative diseases. (C) 2013 Elsevier Inc. All rights reserved.