Costa Lucio G, de Laat Rian, Dao Khoi, Pellacani Claudia, Cole Toby B, Furlong Clement E
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Department of Neuroscience, University of Parma, Italy.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Neurotoxicology. 2014 Jul;43:3-9. doi: 10.1016/j.neuro.2013.08.011. Epub 2013 Sep 4.
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.
对氧磷酶2（PON2）是一个基因家族的成员，该家族还包括研究较多的对氧磷酶1（PON1）以及对氧磷酶3（PON3）。PON2在这三种对氧磷酶中独具特色，因为它在脑组织中表达。PON2是一种内酯酶，具有抗氧化和抗炎特性。PON2水平在多巴胺能区域（如纹状体）最高，在星形胶质细胞中高于神经元，并且在雌性小鼠的脑和外周组织中高于雄性小鼠。在亚细胞水平上，PON2主要定位于线粒体，在那里它清除超氧化物。缺乏PON2（如在PON2基因敲除小鼠中）或PON2水平较低（如雄性小鼠与雌性小鼠相比）会增加对氧化应激诱导毒性的易感性。雌二醇在体外和体内均可增加PON2的表达，并提供针对氧化应激的神经保护作用。在PON2基因敲除小鼠的中枢神经系统细胞中不存在这种神经保护作用。用多酚槲皮素也能得到类似结果。鉴于PON2的细胞定位及其抗氧化和抗炎作用，它可能是一种参与神经保护的相关酶，并且可能代表神经保护策略的一个新靶点。它在雄性和雌性中的差异表达可能解释了包括神经发育、神经和神经退行性疾病在内的各种疾病发病率的性别差异。
