Department of Nutrition, College of Health Care, China Medical University, Taichung, Taiwan.
Toxicol Lett. 2010 May 4;194(3):70-8. doi: 10.1016/j.toxlet.2010.02.003. Epub 2010 Feb 11.
Mercury, one of the widespread pollutants in the world, induces oxidative stress and dysfunction in many cell types. Alveolar type II epithelial cells are known to be vulnerable to oxidative stress. Alveolar type II epithelial cells produce and secrete surfactants to maintain morphological organization, biophysical functions, biochemical composition, and immunity in lung tissues. However, the precise action and mechanism of mercury on alveolar type II epithelial cell damage remains unclear. In this study, we investigate the effect and possible mechanism of methylmercury chloride (MeHgCl) on the human lung invasive carcinoma cell line (Cl1-0) and mouse lung tissue. Cl1-0 cells were exposed to MeHgCl (2.5-10 microM) for 24-72 h. The results showed a decrease in cell viability and an increase in malondialdehyde (MDA) level and ROS production at 72 h after MeHgCl exposure in a dose-dependent manner. Caspase-3 activity, sub-G1 contents and annexin-V binding were dramatically enhanced in Cl1-0 cells treated with MeHgCl. MeHgCl could also activate Bax, release cytochrome c, and cleave poly(ADP-Ribose) polymerase (PARP), and decrease surfactant proteins mRNA levels. Moreover, in vivo study showed that mercury contents of blood and lung tissues were significantly increased after MeHgCl treatment in mice. The MDA levels in plasma and lung tissues were also dramatically raised after MeHgCl treatment. Lung tissue sections of MeHgCl-treated mice showed pathological fibrosis as compared with vehicle control. The mRNA levels of proteins in apoptotic signaling, including p53, mdm-2, Bax, Bad, and caspase-3 were increased in mice after exposure to MeHgCl. In addition, the mRNA levels of surfactant proteins (SPs), namely, SP-A, SP-B, SP-C, and SP-D (alveolar epithelial cell functional markers) were significantly decreased. These results suggest that MeHgCl activates an oxidative stress-induced mitochondrial cell death in alveolar epithelial cells.
汞是世界上广泛存在的污染物之一，可诱导许多细胞类型的氧化应激和功能障碍。肺泡 II 型上皮细胞已知易受氧化应激影响。肺泡 II 型上皮细胞产生和分泌表面活性剂，以维持肺组织的形态组织、生物物理功能、生化组成和免疫。然而，汞对肺泡 II 型上皮细胞损伤的确切作用和机制尚不清楚。在这项研究中，我们研究了甲基汞氯化物（MeHgCl）对人肺浸润性癌细胞系（Cl1-0）和小鼠肺组织的影响及其可能的机制。Cl1-0 细胞暴露于 MeHgCl（2.5-10 microM）24-72 h。结果显示，MeHgCl 暴露 72 h 后，细胞活力下降，丙二醛（MDA）水平和 ROS 产生增加，呈剂量依赖性。Cl1-0 细胞中 caspase-3 活性、Sub-G1 含量和 Annexin-V 结合明显增强。MeHgCl 还可以激活 Bax，释放细胞色素 c，切割聚（ADP-核糖）聚合酶（PARP），并降低表面活性蛋白 mRNA 水平。此外，体内研究表明，小鼠经 MeHgCl 处理后血液和肺组织中的汞含量明显增加。MeHgCl 处理后血浆和肺组织中的 MDA 水平也显著升高。与载体对照组相比，MeHgCl 处理的小鼠肺组织切片显示出病理性纤维化。暴露于 MeHgCl 后，小鼠凋亡信号蛋白（包括 p53、mdm-2、Bax、Bad 和 caspase-3）的 mRNA 水平升高。此外，表面活性蛋白（SPs）的 mRNA 水平，即 SP-A、SP-B、SP-C 和 SP-D（肺泡上皮细胞功能标志物）显著降低。这些结果表明，MeHgCl 激活了肺泡上皮细胞中氧化应激诱导的线粒体细胞死亡。
