Mörbt Nora, Mögel Iljana, Kalkhof Stefan, Feltens Ralph, Röder-Stolinski Carmen, Zheng Jiang, Vogt Carsten, Lehmann Irina, von Bergen Martin
Department of Proteomics, UFZ, Helmholtz-Centre for Environmental Research, Leipzig, Germany.
Proteomics. 2009 Nov;9(21):4920-33. doi: 10.1002/pmic.200800836.
Styrene is a volatile organic compound that is widely used as an intermediate in many industrial settings. There are known adverse health effects at environmentally significant concentrations, but little is known about the molecular effect of exposure to styrene at sub-acute toxic concentrations. We exposed human lung epithelial cells, at a wide range of concentrations (1 mg/m(3)-10 g/m(3)), to styrene and analyzed the effects on the proteome level by 2-DE, where 1380 proteins spots were detected and 266 were identified unambiguously by MS. A set of 16 protein spots were found to be significantly altered due to exposure to styrene at environmentally significant concentrations of 1-10 mg/m(3) (0.2-2.3 ppm). Among these, superoxide dismutase as well as biliverdin reductase A could be correlated with the molecular pathway of oxidative stress, while eukaryotic translation initiation factor 5A-1, ezrin, lamin B2 and voltage-dependent anion channel 2 have been reported to be involved in apoptosis. Treatment with styrene also caused the formation of styrene oxide-protein adducts, specifically for thioredoxin reductase 1. These results underline the relevance of oxidative stress as a primary molecular response mechanism of lung epithelial cells to styrene exposure at indoor-relevant concentrations.
苯乙烯是一种挥发性有机化合物,在许多工业环境中被广泛用作中间体。在对环境有重要影响的浓度下,已知其会对健康产生不良影响,但对于亚急性毒性浓度的苯乙烯暴露的分子效应却知之甚少。我们将人肺上皮细胞暴露于一系列浓度(1毫克/立方米 - 10克/立方米)的苯乙烯中,并通过双向电泳在蛋白质组水平分析其影响,共检测到1380个蛋白质斑点,其中266个通过质谱明确鉴定。发现在环境相关浓度1 - 10毫克/立方米(0.2 - 2.3 ppm)的苯乙烯暴露下,有一组16个蛋白质斑点发生了显著变化。其中,超氧化物歧化酶以及胆绿素还原酶A可能与氧化应激的分子途径相关,而真核翻译起始因子5A - 1、埃兹蛋白、核纤层蛋白B2和电压依赖性阴离子通道2据报道与细胞凋亡有关。苯乙烯处理还导致了环氧苯乙烯 - 蛋白质加合物的形成,特别是针对硫氧还蛋白还原酶1。这些结果强调了氧化应激作为肺上皮细胞在室内相关浓度下暴露于苯乙烯时的主要分子反应机制的相关性。