Mitochondrial proteomic alterations caused by long-term low-dose copper exposure in mouse cortex
Mitochondrial proteomic alterations caused by long-term low-dose copper exposure in mouse cortex
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小鼠皮层长期低剂量铜暴露引起的线粒体蛋白质组改变
DOI：
10.1016/j.toxlet.2016.10.009
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发表时间：
2016-11-30
影响因子：
3.5
通讯作者：
Yang, Xifei
中科院分区：
文献类型：
--
作者：
Lin, Xuemei;Wei, Gang;Yang, Xifei
线粒体功能障碍与暴露于各种化学物质（如铜）引起的神经毒性有关。然而，长期低剂量铜暴露对线粒体蛋白质组的影响尚不清楚。在这项研究中，我们发现铜（0.13 ppm的硫酸铜在饮用水）的治疗12个月造成的异常表达的线粒体蛋白（7上调和6下调），显示了在小鼠皮层的双向电泳结合质谱。蛋白质功能分析表明，这些差异表达的蛋白质主要包括轴突形成相关蛋白、轴突导向相关蛋白、轴突发生相关蛋白和线粒体呼吸链复合体。在这些差异表达的线粒体蛋白中，发现GRP 75（75 kDa葡萄糖调节蛋白）和GRP 78（78 kDa葡萄糖调节蛋白）显着下调，这一点已通过Western印迹分析证实。GRP 75的下调显示促进凋亡。GRP 78/BiP的下调可上调内质网（ER）应激介质，从而引起细胞凋亡。我们的研究表明，这些差异表达的线粒体蛋白，如GRP 75和GRP 78可能参与了长期低剂量铜暴露引起的神经毒性，并作为潜在的分子靶点，为铜神经毒性的治疗。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Mitochondrial dysfunction is involved in neurotoxicity caused by exposure of various chemicals such as copper. However, the effects of long-term low-dose copper exposure on mitochondrial proteome remain unclear. In this study, we found the treatment of copper (0.13 ppm copper sulfate in drinking water) for 12 months caused abnormal expression of a total of 13 mitochondrial proteins (7 up-regulated and 6 downregulated) as revealed by two-dimensional electrophoresis coupled with mass spectrometry in mouse cortex. Protein functional analysis revealed that these differentially expressed proteins mainly included apoptosis-associated proteins, axon guidance-associated proteins, axonogenesis-associated proteins and mitochondrial respiratory chain complex. Among these differentially expressed mitochondrial proteins, GRP75 (75 kDa glucose-regulated protein) and GRP78 (78 kDa glucose-regulated protein) were found to be significantly down-regulated as confirmed by Western-blot analysis. The down-regulation of GRP75 was shown to promote apoptosis. The down-regulation of GRP78/BiP could up-regulate endoplasmic reticulum (ER) stress mediators and thus cause apoptosis. Our study suggested that these differentially expressed mitochondrial proteins such as GRP75 and GRP78 could be involved in neurotoxicity caused by long-term low-dose copper exposure and serve as potential molecular targets for the treatment of copper neurotoxicity. (C) 2016 Elsevier Ireland Ltd. All rights reserved.