Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells.
Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells.
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通过抗体阵列分析人支气管上皮细胞中镉诱导的细胞凋亡的蛋白质组分析。
DOI：
10.18632/oncotarget.6738
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发表时间：
2016-02-02
期刊：
影响因子：
--
通讯作者：
Lau AT
中科院分区：
文献类型：
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作者：
Xu YM;Wu DD;Zheng W;Yu FY;Yang F;Yao Y;Zhou Y;Ching YP;Lau AT
蛋白质阵列技术是一个强大的平台，可同时测定多种蛋白质的表达水平以及磷酸化等翻译后修饰。在这里，我们首次通过抗体阵列分析筛选并报告了镉（Cd）诱导人支气管上皮细胞（BEAS-2B）细胞毒性过程中的主要信号级联和凋亡介质。 Proteome Profiler™ 阵列捕获对照细胞和镉处理细胞的蛋白质，用于平行测定蛋白质磷酸化和与细胞凋亡相关的蛋白质的相对水平。我们的结果表明，Cd 处理显着激活了 p38 MAPK 和 JNK 相关信号转导途径。 Cd 有效刺激 p38α (MAPK14)、JNK1/2 (MAPK8/9) 和 JUN 的磷酸化；而 Akt1、ERK1/2 (MAPK3/1)、GSK3β 和 mTOR 的磷酸化则受到抑制。此外，还诱导促凋亡蛋白 BAX、线粒体释放细胞色素 c (CYCS)、激活 caspase-3/9 (CASP3/9)；以及细胞周期检查点蛋白（TP53、p21 和 p27）和几种凋亡蛋白抑制剂 (IAP) [包括 cIAP-1/2 (BIRC2/3)、XIAP (BIRC4) 和 survivin (BIRC5)] 表达降低。在 Cd 处理之前用硫醇抗氧化剂谷胱甘肽或 p38 MAPK/JNK 抑制剂预处理细胞可有效消除 p38 MAPK/JNK 通路和凋亡相关蛋白的 ROS 激活。综上所述，我们的结果表明，Cd 会导致氧化应激诱导的细胞凋亡；在镉暴露的人肺细胞中，p38 MAPK/JNK和线粒体途径更重要地参与信号转导和诱导细胞凋亡。
Protein array technology is a powerful platform for the simultaneous determination of the expression levels of a number of proteins as well as post-translational modifications such as phosphorylation. Here, we screen and report for the first time, the dominant signaling cascades and apoptotic mediators during the course of cadmium (Cd)-induced cytotoxicity in human bronchial epithelial cells (BEAS-2B) by antibody array analyses. Proteins from control and Cd-treated cells were captured on Proteome Profiler™ Arrays for the parallel determination of the relative levels of protein phosphorylation and proteins associated with apoptosis. Our results indicated that the p38 MAPK- and JNK-related signal transduction pathways were dramatically activated by Cd treatment. Cd potently stimulates the phosphorylations of p38α (MAPK14), JNK1/2 (MAPK8/9), and JUN; while the phosphorylations of Akt1, ERK1/2 (MAPK3/1), GSK3β, and mTOR were suppressed. Moreover, there was an induction of proapoptotic protein BAX, release of cytochrome c (CYCS) from mitochondria, activation of caspase-3/9 (CASP3/9); as well as decreased expression of cell cycle checkpoint proteins (TP53, p21, and p27) and several inhibitors of apoptosis proteins (IAPs) [including cIAP-1/2 (BIRC2/3), XIAP (BIRC4), and survivin (BIRC5)]. Pretreatment of cells with the thiol antioxidant glutathione or p38 MAPK/JNK inhibitors before Cd treatment effectively abrogated ROS activation of p38 MAPK/JNK pathways and apoptosis-related proteins. Taken together, our results demonstrate that Cd causes oxidative stress-induced apoptosis; and the p38 MAPK/JNK and mitochondrial pathways are more importantly participated for signal transduction and the induction of apoptosis in Cd-exposed human lung cells.