Cellular Response of Fusarium oxysporum to Crocidolite Asbestos As Revealed by a Combined Proteomic Approach

Cellular mechanisms of asbestos toxicity rely, at least in part, on the chemical composition of these minerals. Iron ions are directly involved in the accepted mechanism of fiber toxicity because they constitute active centers where release of free radicals and reactive oxygen species takes place. Although no current technology is available for the remediation of asbestos polluted sites, the soil fungus Fusarium oxysporum was found to be very effective in iron extraction from crocidolite asbestos in vitro, and to cause a significant reduction in asbestos surface reactivity and oxidative damage to naked DNA. As little information is available on the molecular mechanisms of the fungus−asbestos interactions, a combined proteomic approach that used 2-DE, shotgun and quantitative iTRAQ proteomics was used to investigate the fungal metabolic activities in the presence of crocidolite, an iron-rich type of asbestos. Although global proteomic analyses did not show significant changes in the protein expression pattern of F. oxysporum when exposed to asbestos fibers, some proteins specifically regulated by asbestos suggest up-regulation of metabolic pathways involved in protection from oxidative stress. When compared with the response to crocidolite observed by other authors in human lung epithelial cells, that unlike fungi can internalize the asbestos fibres, a significant difference was the regulation of the pentose phosphate pathway.

细胞学机制在石棉毒性的作用中，至少部分依赖于这些矿物的化学组成。铁离子直接参与了纤维毒性的公认机制，因为它们构成了释放自由基和活性氧的活性中心。尽管目前尚无技术可用于修复石棉污染场地，但研究发现土壤真菌Fusarium oxysporum在体外从青石棉中提取铁元素方面非常有效，并且能够显著降低石棉表面对裸露DNA的氧化损伤和反应活性。鉴于关于真菌-石棉相互作用分子机制的资料甚少，研究者采用了一种结合二维电泳（2-DE）、鸟枪法质谱和定量iTRAQ蛋白质组学的蛋白质组学方法，以研究真菌在青石棉（一种富含铁的纤维状石棉）存在条件下的代谢活性。尽管全局蛋白质组学分析并未显示出F. oxysporum在暴露于石棉纤维时蛋白质表达模式的显著变化，但一些由石棉特异性调控的蛋白质暗示了参与抗氧化应激保护代谢途径的上调。与其他研究者观察到的青石棉在人类肺上皮细胞中的反应相比，真菌不能内化石棉纤维，一个显著的区别在于戊糖磷酸途径的调控。