Boatti Lara, Robotti Elisa, Marengo Emilio, Viarengo Aldo, Marsano Francesco
Department of Science & Technological Innovation (DiSIT), The University of Eastern Piedmont Amedeo Avogadro, Alessandria, Novara, Vercelli, Viale Teresa Michel, 11-15121 Alessandria, Italy.
Int J Mol Sci. 2012 Nov 23;13(12):15679-705. doi: 10.3390/ijms131215679.
Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC) of 25% and 50% and their binary mixture (Ec25 + EC25) on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS). We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE) proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes.
化学物质混合物可能具有相加、协同或拮抗相互作用。我们基于溶酶体膜稳定性(LMS),研究了暴露于镍、效应浓度(EC)为25%和50%的有机磷酸酯杀虫剂毒死蜱及其二元混合物(Ec25 + EC25)对盘基网柄菌变形虫的影响。我们在受控实验室条件下用这些化合物处理盘基网柄菌,并使用二维凝胶电泳(2DE)蛋白质组学方法评估蛋白质水平的变化。在EC25浓度下用镍处理诱导了14个蛋白质斑点的变化,其中12个下调。在EC50浓度下用镍处理导致15个斑点发生变化,其中10个下调。在EC25浓度下用毒死蜱处理诱导了6个斑点的变化,所有这些斑点均下调;在EC50浓度下用毒死蜱处理诱导了13个斑点的变化,其中5个下调。每种化合物的EC25对应的混合物诱导了19个斑点的变化,其中13个下调。这些数据共同表明,每种处理都存在不同的蛋白质表达特征,并且只有少数蛋白质在多种不同处理中受到调节。对于简单的二元混合物,蛋白质组学反应无法识别每种毒物。通过质谱鉴定了显示出显著差异的蛋白质斑点,结果揭示了参与金属解毒、应激适应、氧化应激反应和其他细胞过程的蛋白质的调节情况。