4.3 Article

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

期刊

ONCOTARGET
卷 7, 期 5, 页码 6146-6158

出版社

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6738

关键词

cadmium; human lung cells; antibody array; post-translational modifications; mitochondrial pathway

资金

  1. National Natural Science Foundation of China [31170785, 81101785, 30870497, 31271445]
  2. Fund for University Talents of Guangdong Province
  3. Guangdong Natural Science Foundation of China [S2012030006289]
  4. Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases

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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.

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