Arsenite is well documented as a chemotherapeutic agent capable of inducing cell death. However, the cellular response at the molecular level has not been studied extensively. In the present study, we provide for the first time a proteomic analysis of rat LECs (lung epithelial cells) treated with arsenite, with the aim of identifying defence proteins, probably expressed to protect the cells during the course of arsenic-induced apoptosis. Comparative proteome analysis was conducted on LECs and LECs treated with 40 μM arsenite to identify global changes in their protein expression profiles. Over 1000 protein spots were separated by two-dimensional electrophoresis and visualized by silver staining. Seven proteins changed expression levels significantly and were identified by matrix-assisted laser-desorption ionization–time-of-flight mass spectrometry and database searching. The proteins up-regulated were mostly HSPs (heat-shock proteins) and antioxidative stress proteins, including HSP70, aldose reductase, haem oxygenase-1, HSP27, ferritin light chain and αB-crystallin. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase was down-regulated. Pretreatment with the thiol antioxidants glutathione or N-acetylcysteine before arsenite insult effectively abrogated the induction of these defence proteins and sustained cell viability, whereas antioxidants were protective only at earlier time points if they were added to cells after arsenite. Taken together, our results demonstrate that high levels of arsenite cause oxidative stress-induced apoptosis.
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Research Article|
August 24 2004
A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis
Andy T. Y. LAU;
Andy T. Y. LAU
*Institute of Molecular Biology, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
†Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
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Qing-Yu HE;
Qing-Yu HE
†Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
‡Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
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Jen-Fu CHIU
Jen-Fu CHIU
1
*Institute of Molecular Biology, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
†Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, People's Republic of China
1To whom correspondence should be addressed (email jfchiu@hkucc.hku.hk).
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Publisher: Portland Press Ltd
Received:
February 10 2004
Revision Received:
May 10 2004
Accepted:
June 03 2004
Accepted Manuscript online:
June 03 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 382 (2): 641–650.
Article history
Received:
February 10 2004
Revision Received:
May 10 2004
Accepted:
June 03 2004
Accepted Manuscript online:
June 03 2004
Citation
Andy T. Y. LAU, Qing-Yu HE, Jen-Fu CHIU; A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem J 1 September 2004; 382 (2): 641–650. doi: https://doi.org/10.1042/BJ20040224
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