Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.
Free Radic Biol Med. 2022 Jan;178:215-218. doi: 10.1016/j.freeradbiomed.2021.12.005. Epub 2021 Dec 7.
Mitochondrial dysfunction and oxidative stress contribute to the neuropathology of neurodegenerative disorders such as Parkinson's disease (PD). Paraoxonase-2 (PON2) is a mitochondrial protein that mitigates oxidative stress, enhances mitochondrial function and exhibits anti-inflammatory properties. Previously, we have documented sex-based variation in PON2 with higher brain PON2 expression in female (2-fold) as compared to male African green monkeys. This aim of this study is to identify PON2 isoforms and explore the region-based variations in the protein level of PON2 in brain of African green monkeys. Male and female brain tissue samples (striatum, hippocampus, occipital cortex, dorsolateral prefrontal cortex) from African green monkeys (Chlorocebus sabaeus) were analyzed by western blotting technique for PON2 expression. We found two PON2 isoforms (39 and 41 kDa) in each examined brain region of male and female monkeys. Male monkeys showed no significant difference in the expression level of PON2 isoforms among different brain regions whereas female monkeys showed a significant difference in the expression level of PON2 isoforms in all examined regions except dorsolateral prefrontal cortex. In addition, the result revealed highest expression of PON2 protein in striatum compared to other brain regions in both male and female monkeys. This report is the first to quantify expression of PON2 isoforms in different brain regions and it also establishes the existence of sex as well as region-based variation in PON2 protein expression in primate brain. Since PON2 serves a protective role for dopaminergic neurons it should be considered as a druggable target for oxidative stress-related neurodegenerative disorders like PD. We anticipate that the outcome of this study will contribute to the development of neuroprotective strategies in PD.
线粒体功能障碍和氧化应激是导致神经退行性疾病（如帕金森病）神经病理学的原因。对氧磷酶 2（PON2）是一种线粒体蛋白，可减轻氧化应激、增强线粒体功能并具有抗炎特性。之前，我们已经记录了 PON2 的性别差异，与雄性非洲绿猴相比，雌性非洲绿猴大脑中的 PON2 表达更高（2 倍）。本研究的目的是鉴定 PON2 同工型，并探索非洲绿猴大脑中 PON2 蛋白水平的区域差异。使用蛋白质印迹技术分析来自非洲绿猴（Chlorocebus sabaeus）的雄性和雌性脑组织样本（纹状体、海马体、枕叶皮层、背外侧前额叶皮层）中的 PON2 表达。我们在每个被检查的雄性和雌性猴子的脑区中发现了两种 PON2 同工型（39 和 41 kDa）。雄性猴子在不同脑区的 PON2 同工型表达水平没有显著差异，而雌性猴子在所有被检查的脑区（除背外侧前额叶皮层外）的 PON2 同工型表达水平有显著差异。此外，结果显示 PON2 蛋白在纹状体中的表达量最高，其次是其他脑区，无论雄性还是雌性猴子均如此。这是首次在不同脑区定量表达 PON2 同工型的报告，它还确定了 PON2 蛋白在灵长类动物大脑中的表达存在性别差异和区域差异。由于 PON2 对多巴胺能神经元具有保护作用，因此它应被视为与氧化应激相关的神经退行性疾病（如帕金森病）的潜在治疗靶点。我们预计这项研究的结果将有助于开发帕金森病的神经保护策略。
