title: Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells.
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.
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Xu
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wu
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Fei-Yuan
authors.initials: FY
authors.lastname: Yu
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
authors.forename: Yick-Pang
authors.initials: YP
authors.lastname: Ching
authors.affiliation: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors.forename: Andy T Y
authors.initials: AT
authors.lastname: Lau
mesh_terms: D000906:Antibodies / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002105:Cadmium Poisoning / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D040081:Protein Array Analysis / Q000379:methods; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D020543:Proteome; D002104:Cadmium
keywords: antibody array; cadmium; human lung cells; mitochondrial pathway; post-translational modifications