Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells
Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells
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DOI：
10.1007/s11064-020-03173-1
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发表时间：
2020-11
影响因子：
4.4
通讯作者：
Biao Xiang;Daowen Li;Yiqiang Chen;Meng Li;Yuan Zhang;T. Sun;Shusheng Tang
中科院分区：
文献类型：
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作者：
Biao Xiang;Daowen Li;Yiqiang Chen;Meng Li;Yuan Zhang;T. Sun;Shusheng Tang
铜的稳态受损与神经退行性疾病的不同病理生理机制有关，氧化损伤被认为是主要机制。本研究旨在利用姜黄素（一种广泛使用的抗氧化和抗凋亡剂）在体外发挥抗铜的神经保护作用，并阐明其潜在机制。姜黄素的作用通过使用细胞计数试剂盒-8测定、流式细胞术、免疫荧光、分光光度计和蛋白质印迹法来检测。结果表明，姜黄素预处理3 h后，铜诱导的细胞毒性和细胞凋亡均明显降低。进一步的实验表明，姜黄素不仅降低了ROS和MDA的产生，而且提高了ROS清除酶SOD和CAT的活性，减轻了铜诱导的线粒体膜电位下降和细胞色素c核转位。在姜黄素存在下，caspase 3、caspase 9和PARP 1蛋白水平上调，Bax/Bcl-2比值下调。综上所述，我们的研究表明，姜黄素对SH-SY 5 Y细胞中的铜具有神经保护作用，其潜在机制可能与氧化应激和线粒体凋亡有关。
Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot. Results revealed that after pretreatment with curcumin for 3 h, copper-induced toxicity and apoptosis show a significant decline. Further experiments showed that curcumin not only decreased the production of ROS and MDA but also increased the activities of the ROS scavenging enzymes SOD and CAT. Moreover, curcumin treatment alleviated the decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c induced by copper. The protein levels of pro-caspase 3, pro-caspase 9, and PARP1 were up-regulated and the Bax/Bcl-2 ratio was down-regulated in the presence of curcumin. Taken together, our study demonstrates that curcumin has neuroprotective properties against copper in SH-SY5Y cells and the potential mechanisms might be related to oxidative stress and mitochondrial apoptosis.