Proteomic analysis of cadmium exposure in cultured lung epithelial cells: evidence for oxidative stress-induced cytotoxicity

Human exposures to cadmium (Cd) compounds are common in the living environment. Cd is toxic, yet, little is known about its effect at the lung cell proteome level. Here, we provide a proteomic analysis of lung epithelial cells (LECs) treated with CdCl2, with the aim of identifying protein response to Cd toxicity. Comparative proteome analysis was conducted to identify global changes in the protein expression profiles of sham-exposed and Cd-treated cells. Proteins were separated by two-dimensional electrophoresis and visualized by silver staining. We reported that while a low level (2 mu M) of Cd treatment elicited negligible cytotoxicity and produced no significant proteome changes between the treated group and the control, however, a high level (20 mu M) of Cd treatment induced obvious proteome changes and cell death in LECs. Differentially-expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database searching. The proteins that were significantly up-regulated included heat-shock proteins (HSPs) and antioxidative stress proteins. Pretreatment with the thiol antioxidant glutathione before Cd treatment effectively abrogated the induction of these proteins and prevented cell death. Our results demonstrate that Cd causes oxidative stress-induced cell death, and these differentially-expressed proteins are defense proteins important for fighting against the Cd toxicity, while a low level of Cd may exert a more noticeable effect after long-term exposure, but not after transient exposure.