Oncotarget

Research Papers:

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

Yan-Ming Xu, Dan-Dan Wu, Wei Zheng, Fei-Yuan Yu, Feng Yang, Yue Yao, Yuan Zhou, Yick-Pang Ching and Andy T. Y. Lau _

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Oncotarget. 2016; 7:6146-6158. https://doi.org/10.18632/oncotarget.6738

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Abstract

Yan-Ming Xu1, Dan-Dan Wu1,*, Wei Zheng1,*, Fei-Yuan Yu1, Feng Yang1, Yue Yao1, Yuan Zhou2, Yick-Pang Ching2, Andy T. Y. Lau1

1Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, P. R. China

2School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China

*These authors contributed equally to this work

Correspondence to:

Andy T. Y. Lau, e-mail: andytylau@stu.edu.cn

Keywords: cadmium, human lung cells, antibody array, post-translational modifications, mitochondrial pathway

Received: May 19, 2015     Accepted: December 08, 2015     Published: December 23, 2015

ABSTRACT

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.


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