Proteomic analysis of chromium cytotoxicity in cultured rat lung epithelial cells.
Chromium (Cr) has been widely used in industry for more than one century. Exposure to hexavalent Cr compounds is strongly associated with increasing risk of lung cancer. Extensive researches at DNA level indicated that generation of ROS from the reduction of Cr(VI) leading to DNA damage is the major cause of the toxicity and carcinogenicity of Cr(VI). The present study in cellular and protein levels confirmed that Cr(VI) induced apoptosis of lung epithelial cells (LEC) via ROS generation. To view the differentially expressed proteins in the process of Cr(VI) reduction, subcellular proteomics was applied and allowed the identification of more than 30 proteins with expression alteration. Most of those proteins are correlated with ROS-elicited responses, which were further validated by Western blotting analysis, induction of p53 pathway and antioxidative treatment. The current findings provided additional evidence in protein level to support the claim that ROS generated during the process of Cr(VI) reduction are involved in the Cr(VI)-induced toxicity and carcinogenesis.
Lei
Ting
T
Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
He
Qing-Yu
QY
Cai
Zhen
Z
Zhou
Yuan
Y
Wang
Yi-Li
YL
Si
Lu-Sheng
LS
Cai
Zongwei
Z
Chiu
Jen-Fu
JF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D002857:Chromium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005456:Fluorescent Dyes / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D009284:Naphthols / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010449:Peptide Mapping; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016622:Silver Staining; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D005456:Fluorescent Dyes; D007211:Indoles; D009284:Naphthols; D017382:Reactive Oxygen Species; D002857:Chromium; C007293:DAPI