Proteomic analysis of cadmium exposure in cultured lung epithelial cells: evidence for oxidative stress-induced cytotoxicity
Proteomic analysis of cadmium exposure in cultured lung epithelial cells: evidence for oxidative stress-induced cytotoxicity
复制标题
培养肺上皮细胞镉暴露的蛋白质组学分析：氧化应激诱导细胞毒性的证据
DOI：
10.1039/c3tx50014d
复制
发表时间：
2013-01-01
影响因子：
2.1
通讯作者：
Lau, Andy T. Y.
中科院分区：
文献类型：
--
作者：
Xu, Yan-Ming;Zhou, Yuan;Lau, Andy T. Y.
人类暴露于镉（Cd）化合物在生活环境中是常见的。镉是有毒的，然而，很少有人知道它在肺细胞蛋白质组水平的影响。在这里，我们提供了一个蛋白质组学分析与氯化镉处理的肺上皮细胞（LEC），目的是确定蛋白质响应镉毒性。进行比较蛋白质组分析，以确定全球变化的蛋白质表达谱的假暴露和镉处理的细胞。通过双向电泳分离蛋白质，并通过银染色可视化。低浓度（2 μM）Cd处理引起的细胞毒性可忽略不计，且处理组与对照组之间蛋白质组无明显变化，而高浓度（20 μM）Cd处理引起LEC蛋白质组明显变化和细胞死亡。通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）和数据库检索鉴定差异表达蛋白。显著上调的蛋白质包括热休克蛋白（HSPs）和抗氧化应激蛋白。预处理与巯基抗氧化剂谷胱甘肽镉治疗前有效地废除了这些蛋白质的诱导，并防止细胞死亡。我们的研究结果表明，镉导致氧化应激诱导的细胞死亡，这些差异表达的蛋白是防御蛋白对抗镉毒性的重要，而低水平的镉可能会产生更明显的影响后，长期暴露，但不是短暂暴露后。
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 μM) of Cd treatment elicited negligible cytotoxicity and produced no significant proteome changes between the treated group and the control, however, a high level (20 μM) 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.