Expression of PON2 isoforms varies among brain regions in male and female African green monkeys.
Expression of PON2 isoforms varies among brain regions in male and female African green monkeys.
复制标题
在男性和女性非洲绿猴中，PON2同工型的表达在大脑区域之间有所不同。
DOI：
10.1016/j.freeradbiomed.2021.12.005
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发表时间：
2022-01
影响因子：
7.4
通讯作者：
Elsworth JD
中科院分区：
文献类型：
--
作者：
Jamwal S;Blackburn JK;Elsworth JD
线粒体功能障碍和氧化应激导致神经退行性疾病如帕金森病（PD）的神经病理学。对氧磷酶-2（PON 2）是一种线粒体蛋白，可减轻氧化应激，增强线粒体功能并表现出抗炎特性。以前，我们已经记录了PON 2的性别差异，雌性（2倍）的大脑PON 2表达高于雄性非洲绿色猴。本研究的目的是鉴定非洲绿色猴脑中的PON 2亚型，并探讨其蛋白水平的区域差异。通过蛋白质印迹技术分析来自非洲绿色猴（Chlorocebus sabaeus）的雄性和雌性脑组织样品（纹状体、海马、枕叶皮质、背外侧前额叶皮质）的PON 2表达。我们发现两个PON 2亚型（39和41 kDa）在每个检查的大脑区域的男性和女性猴子。雄猴不同脑区PON 2亚型的表达水平无显著差异，而雌猴除背外侧前额叶皮质外，其余脑区PON 2亚型的表达水平均存在显著差异。此外，结果显示，与雄性和雌性猴子的其他大脑区域相比，纹状体中的PON 2蛋白表达最高。这份报告是第一个定量的PON 2亚型在不同的大脑区域的表达，它也建立了性别的存在，以及基于区域的变化，PON 2蛋白表达在灵长类动物的大脑。由于PON 2对多巴胺能神经元具有保护作用，因此应将其视为氧化应激相关神经退行性疾病（如PD）的可药用靶标。我们期望这项研究的结果将有助于PD神经保护策略的发展。
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 stratergies in PD.
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影响因子：
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通讯作者：
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通讯作者：
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作者：
Jamwal S;Blackburn JK;Elsworth JD
通讯作者：
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