Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells

被引:21
|
作者
Xu, Yan-Ming [1 ]
Wu, Dan-Dan [1 ]
Zheng, Wei [1 ]
Yu, Fei-Yuan [1 ]
Yang, Feng [1 ]
Yao, Yue [1 ]
Zhou, Yuan [2 ]
Ching, Yick-Pang [2 ]
Lau, Andy T. Y. [1 ]
机构
[1] Shantou Univ, Coll Med, Dept Cell Biol & Genet, Lab Canc Biol & Epigenet, Shantou 515041, Guangdong, Peoples R China
[2] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
cadmium; human lung cells; antibody array; post-translational modifications; mitochondrial pathway; OXIDATIVE STRESS; MALIGNANT-TRANSFORMATION; HEME OXYGENASE-1; CYTOTOXICITY; EXPRESSION; CLUSTERIN; EXPOSURE; PATHWAY;
D O I
10.18632/oncotarget.6738
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 T 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 p38a (MAPK14), JNK1/2 (MAPK8/9), and JUN; while the phosphorylations of Akt1, ERK1/2 (MAPK3/1), GSK3, 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.
引用
收藏
页码:6146 / 6158
页数:13
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