DHA and vitamin E antagonized the A beta 25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells
DHA and vitamin E antagonized the A beta 25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells
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DHA 和维生素 E 通过激活 Nrf2 信号通路和调节 PC12 细胞中 CD36、SRB1 和 FABP5 的表达来拮抗 A beta 25-35 介导的神经元氧化损伤
DOI：
10.1039/c8fo01713a
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Yuan Linhong
中科院分区：
文献类型：
--
作者：
Huang Xiaochen;Zhen Jie;Dong Shengqi;Zhang Huiqiang;Van Halm-Lutterodt Nicholas;Yuan Linhong
本研究旨在探讨二十二碳六烯酸(DHA)和/或维生素E(VE)的体外神经保护作用。用DHA和/或VE处理PC12细胞4h后，再用50μ摩尔L−1 Aβ25-35处理48h，收集细胞并用于氧化应激参数的测定。应用实时定量聚合酶链式反应和蛋白质印迹技术检测脂肪酸转运蛋白、Nrf2及其下游抗氧化靶标基因和蛋白的表达。我们的结果表明，Aβ25-35处理抑制了细胞的生长，增加了细胞内ROS的产生，降低了线粒体膜电位。Aβ25-35处理降低了神经细胞的总抗氧化能力，而升高了丙二醛水平。VE或DHA可拮抗Aβ25-35介导的细胞生长抑制和线粒体膜电位下降。在DHA-和DHA+VE处理的细胞中，观察到Nrf2信号通路的激活和CD36、SRB1和FABP5表达的调节。我们的结果表明，DHA和VE在拮抗Aβ25-35所致的PC12细胞氧化损伤中具有协同作用。本研究的结果将为DHA和VE的营养干预在预防神经元损伤相关疾病中的应用提供参考。
The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 μmol L−1 Aβ25–35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets’ gene and protein expression. Our results indicated that the Aβ25–35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aβ25–35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aβ25–35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aβ25–35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.