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首页> 美国卫生研究院文献>other >Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages
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Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages

机译：小鼠巨噬细胞对二氧化钛和氧化铜纳米粒子的分子响应的比较蛋白质组学分析揭示了巨噬细胞中氧化铜纳米粒子的一些毒性机制。

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Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.
机译：二氧化钛和氧化铜纳米颗粒由于其催化性能，其光吸收性能（二氧化钛）或它们的杀生物性能（氧化铜）而越来越广泛地被使用，从而增加了不利健康影响的风险。在此框架中，研究了小鼠巨噬细胞的反应。进行了蛋白质组学和靶向分析，以研究几个参数，例如吞噬能力，​​细胞因子释放，铜释放和亚毒性剂量下的反应。除二氧化钛和氧化铜纳米颗粒外，铜离子还用作对照。我们还表明，细胞中总的铜释放本身不能解释氧化铜纳米颗粒的毒性。另外，铜离子和氧化铜纳米粒子，而不是氧化钛，都诱导巨噬细胞中的DNA链断裂。至于功能性反应，吞噬能力不受任何无毒剂量处理的影响，而铜离子降低了脂多糖诱导的细胞因子和一氧化氮的产生。蛋白质组学分析强调了由二氧化钛纳米颗粒诱导的变化非常少，但是对血红素氧化酶的诱导，谷胱甘肽合成的增加和对氧化铜纳米颗粒的响应的四氢生物蝶呤的减少。随后的针对性分析表明，谷胱甘肽生物合成的增加和血红素加氧酶的诱导（例如，洛伐他汀/莫纳可林K的诱导）对于巨噬细胞在铜攻击中生存至关重要，并且儿茶酚胺途径的中间体可与氧化铜产生强烈的交叉毒性。纳米粒子和铜离子。

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