Drake Matthew G, Witzmann Frank A, Hyde Juanita, Witten Mark L
Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, Arizona Health Sciences Center, 1501 N Campbell Avenue, Room 3354, Tucson, AZ 85724, USA.
Toxicology. 2003 Sep 30;191(2-3):199-210. doi: 10.1016/s0300-483x(03)00251-8.
The purpose of this study was to investigate the proteomic mechanisms of Jet Propulsion-8 (JP-8) toxicity in the lung, specifically relating to lung epithelial cell apoptosis and edema. Male Swiss-Webster mice were exposed to 1 h/day aerosolized JP-8 jet fuel at concentrations of 250, 1000, and 2500 mg/m(3) for 7 days. Lung cytosol and whole lung samples were solubilized, separated via large scale, high-resolution two-dimensional electrophoresis, and processed for analysis. Significant quantitative differences in lung protein expression were found as a result of JP-8 exposure. At 250 mg/m(3) JP-8 concentration, 31 proteins exhibited increased expression, while 10 showed decreased expression. At 1000 mg/m(3) exposure levels, 21 lung proteins exhibited increased expression and 99 demonstrated decreased expression. At 2500 mg/m(3), 30 exhibited increased expression, while 135 showed decreased expression. Several of the proteins were identified by peptide mass fingerprinting, and were found to relate to cell structure, cell proliferation, protein repair, and apoptosis. These data demonstrate the significant stress JP-8 jet fuel puts on lung epithelium. Furthermore, there was a decrease in alpha1-anti-trypsin expression suggesting that JP-8 jet fuel exposure may have implications for the development of pulmonary disorders.
本研究的目的是调查喷气推进燃料8(JP - 8)对肺部产生毒性的蛋白质组学机制,特别是与肺上皮细胞凋亡和水肿相关的机制。将雄性瑞士韦伯斯特小鼠每天暴露于浓度为250、1000和2500 mg/m³的雾化JP - 8喷气燃料中1小时,持续7天。将肺胞质溶胶和全肺样本溶解,通过大规模、高分辨率二维电泳进行分离,并进行分析处理。结果发现,JP - 8暴露导致肺蛋白表达出现显著的定量差异。在JP - 8浓度为250 mg/m³时,31种蛋白质表达增加,而10种蛋白质表达减少。在暴露水平为1000 mg/m³时,21种肺蛋白表达增加,99种蛋白表达减少。在2500 mg/m³时,30种蛋白表达增加,135种蛋白表达减少。通过肽质量指纹图谱鉴定了其中几种蛋白质,发现它们与细胞结构、细胞增殖、蛋白质修复和凋亡有关。这些数据表明JP - 8喷气燃料对肺上皮造成了显著的应激。此外,α1 -抗胰蛋白酶表达下降,这表明暴露于JP - 8喷气燃料可能对肺部疾病的发展产生影响。