Garrick Jacqueline M, Dao Khoi, de Laat Rian, Elsworth John, Cole Toby B, Marsillach Judit, Furlong Clement E, Costa Lucio G
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
Chem Biol Interact. 2016 Nov 25;259(Pt B):168-174. doi: 10.1016/j.cbi.2016.04.001. Epub 2016 Apr 7.
Paraoxonase 2 (PON2) is a member of the paraoxonase gene family also comprising PON1 and PON3. PON2 functions as a lactonase and exhibits anti-bacterial as well as antioxidant properties. At the cellular level, PON2 localizes to the mitochondrial and endoplasmic reticulum membranes where it scavenges reactive oxygen species. PON2 is of particular interest as it is the only paraoxonase expressed in brain tissue and appears to play a critical role in mitigating oxidative stress in the brain. The aim of this study was to investigate the expression of PON2 at the protein and mRNA level in the brain and liver of mice through development to identify potential age windows of susceptibility to oxidative stress, as well as to compare expression of hepatic PON2 to expression of PON1 and PON3. Overall, PON2 expression in the brain was lower in neonatal mice and increased with age up to postnatal day (PND) 21, with a significant decrease observed at PND 30 and 60. In contrast, the liver showed continuously increasing levels of PON2 with age, similar to the patterns of PON1 and PON3. PON2 protein levels were also investigated in brain samples from non-human primates, with PON2 increasing with age up to the infant stage and decreasing at the juvenile stage, mirroring the results observed in the mouse brain. These variable expression levels of PON2 suggest that neonatal and young adult animals may be more susceptible to neurological insult by oxidants due to lower levels of PON2 in the brain.
对氧磷酶2（PON2）是对氧磷酶基因家族的成员之一，该家族还包括PON1和PON3。PON2作为一种内酯酶发挥作用，具有抗菌和抗氧化特性。在细胞水平上，PON2定位于线粒体和内质网的膜上，在那里它清除活性氧。PON2特别受关注，因为它是脑组织中唯一表达的对氧磷酶，并且似乎在减轻脑内氧化应激方面起关键作用。本研究的目的是通过发育过程研究小鼠脑和肝脏中PON2在蛋白质和mRNA水平的表达，以确定对氧化应激易感性的潜在年龄窗口期，并比较肝脏中PON2的表达与PON1和PON3的表达。总体而言，新生小鼠脑中的PON2表达较低，在出生后第21天（PND 21）前随年龄增加，在PND 30和60时显著下降。相比之下，肝脏中PON2的水平随年龄持续增加，与PON1和PON3的模式相似。还对来自非人类灵长类动物的脑样本中的PON2蛋白水平进行了研究，结果显示PON2在婴儿期前随年龄增加，在幼年期下降，这与在小鼠脑中观察到的结果一致。PON2这些变化的表达水平表明，新生和年轻成年动物可能因脑中PON2水平较低而更容易受到氧化剂的神经损伤。
