Cell metabolomics reveals the neurotoxicity mechanism of cadmium in PC12 cells
Cell metabolomics reveals the neurotoxicity mechanism of cadmium in PC12 cells
复制标题
细胞代谢组学揭示镉对PC12细胞的神经毒性机制
DOI：
10.1016/j.ecoenv.2017.08.028
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发表时间：
2018
影响因子：
6.8
通讯作者：
Song Fengrui
中科院分区：
文献类型：
--
作者：
Zong Li;Xing Junpeng;Liu Shu;Liu Zhiqiang;Song Fengrui
镉(Cd)等重金属可引起神经毒性。关于Cd对人类健康影响的研究已有广泛报道，但对Cd对中枢神经系统影响的分子机制尚需系统研究。本文采用四甲基偶氮唑蓝(3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑)比色法测定不同浓度的氯化镉对PC-12细胞的细胞毒作用。选择IC15值(15%抑制浓度)进行进一步的机理研究。用IC15cCl2与PC-12细胞孵育48h后，采用超高效液相色谱-四极杆飞行时间质谱仪(UPLC-Q-TOF-MS)细胞代谢组学方法分析细胞内外代谢产物。研究发现，重金属Cd对PC-12细胞活力的影响呈剂量依赖性。代谢变化涉及糖酵解和糖异生、生物蝶呤代谢、色氨酸代谢、酪氨酸代谢、甘油磷脂代谢和脂肪酸β-氧化。这些都会引起细胞膜的扰动、氧化还原平衡、能量供应、细胞解毒，进而影响细胞的增殖和凋亡等细胞活动。
The heavy metals such as cadmium (Cd) can induce neurotoxicity. Extensive studies about the effects of Cd on human health have been reported, however, a systematic investigation on the molecular mechanisms of the effects of Cd on central nervous system is still needed. In this paper, the neuronal PC-12 cells were treated with a series of concentrations of CdCl2for 48 h. Then the cytotoxicity was evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. The IC15value (15% inhibiting concentration) was selected for further mechanism studies. After PC-12 cells incubated with CdCl2at a dose of IC15for 48 h, the intracellular and extracellular metabolites were profiled using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based cell metabolomics approach. As found, the effects of the heavy metal Cd produced on the PC-12 cell viability were dose-dependent. The metabolic changes were involved in the glycolysis and gluconeogenesis, biopterin metabolism, tryptophan metabolism, tyrosine metabolism, glycerophospholipid metabolism, and fatty acids beta-oxidation. These could cause the perturbation of cell membrane, redox balance, energy supply, cellular detoxification, further affecting the cellular proliferation and apoptosis and other cellular activities.