Protective effects of xyloketal B against MPP plus -induced neurotoxicity in Caenorhabditis elegans and PC12 cells
Protective effects of xyloketal B against MPP plus -induced neurotoxicity in Caenorhabditis elegans and PC12 cells
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DOI：
10.1016/j.brainres.2010.03.071
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发表时间：
2010-05-21
期刊：
影响因子：
2.9
通讯作者：
Zeng, Jinsheng
中科院分区：
文献类型：
--
作者：
Lu, Xi-lin;Yao, Xiao-li;Zeng, Jinsheng
帕金森病（PD）是第二大常见的神经退行性疾病，影响了2%的65岁以上人口。线粒体缺陷和氧化应激积极参与帕金森病多巴胺能（DA）神经元变性。Xyloketal B是一种从红树林真菌Xylaria sp.中分离得到的具有独特化学结构的新型海洋化合物。2508)。最近，我们已经证明Xyloketal B可以直接清除DPPH自由基并保护线粒体免受氧化损伤。在本研究中，我们研究了木酮B对MPP+诱导的秀丽隐杆线虫和PC12细胞的神经毒性的神经保护作用。研究了秀丽隐杆线虫DA神经元中选择性表达绿色荧光蛋白（GFP）的细胞活力和DA神经退行性变化。采用MTT和核形态学检测PC12细胞损伤。测定细胞内活性氧（ROS）、线粒体膜电位和总谷胱甘肽。木酮B剂量依赖性保护秀丽隐杆线虫抗MPP+诱导的生存能力丧失和DA神经退行性变。类似的神经保护作用在MPP+ PC12细胞模型中得到复制。此外，xyloketal B可减弱MPP+诱导的细胞内ROS积累、线粒体膜电位丧失和恢复PC12细胞总GSH水平。综上所述，本研究表明木酮B主要通过其抗氧化特性和恢复总GSH水平来保护秀丽隐杆线虫和PC12细胞免受MPP+诱导的神经毒性。(C) 2010 Elsevier B.V.版权所有
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population over age 65 years. Mitochondrial defect and oxidative stress actively participate in the dopaminergic (DA) neuron degeneration in PD. Xyloketal B is a novel marine compound with unique chemical structure isolated from mangrove fungus Xylaria sp. (no. 2508). Recently, we have demonstrated that Xyloketal B can directly scavenge DPPH free radicals and protects mitochondria against oxidative insult. In the present study, we investigate the neuroprotective action of xyloketal B against MPP+-induced neurotoxicity in Caenorhabditis elegans and PC12 cells. The viability and DA neurodegeneration was assessed in C. elegans selectively expressing green fluorescent protein (GFP) in DA neurons. PC12 cell damage was measured using MTT and nuclear morphology. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential and total GSH were assessed. Xyloketal B dose-dependently protected against MPP+-induced loss of viability and DA neurodegeneration in C. elegans. Similar neuroprotection was replicated in MPP+ PC12 cell model. In addition, xyloketal B attenuated MPP+-induced intracellular ROS accumulation, loss of mitochondrial membrane potential and restored total GSH level in PC12 cells. All together, the present study demonstrates that xyloketal B protects against MPP+-induced neurotoxicity in C. elegans and PC12 cells mainly through its antioxidant property and restoration of total GSH level. (C) 2010 Elsevier B.V. All rights reserved.