Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währingerstr. 38-40, 1090, Vienna, Austria.
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Währingerstr. 38-40, 1090, Vienna, Austria.
Sci Rep. 2018 Jul 27;8(1):11351. doi: 10.1038/s41598-018-29728-5.
Morphology together with the capability to respond to surrounding stimuli are key elements governing the spatial interaction of living cells with the environment. In this respect, biomechanical stimulation can trigger significant physiological cascades that can potentially modulate toxicity. Deoxynivalenol (DON, vomitoxin) is one of the most prevalent mycotoxins produced by Fusarium spp. and it was used to explore the delicate interaction between biomechanical stimulation and cytotoxicity in A431 cells. In fact, in addition of being a food contaminant, DON is a relevant toxin for several organ systems. The combination between biomechanical stimulation and the mycotoxin revealed how DON can impair crucial functions affecting cellular morphology, tubulin and lysosomes at concentrations even below those known to be cytotoxic in routine toxicity studies. Sub-toxic concentrations of DON (0.1-1 μM) impaired the capability of A431 cells to respond to a biomechanical stimulation that normally sustains trophic effects in these cells. Moreover, the effects of DON (0.1-10 μM) were partially modulated by the application of uniaxial stretching (0.5 Hz, 24 h, 15% deformation). Ultimately, proteomic analysis revealed the potential of DON to alter several proteins necessary for cell adhesion and cytoskeletal modulation suggesting a molecular link between biomechanics and the cytotoxic potential of the mycotoxin.
形态学以及对外界刺激的响应能力是控制活细胞与环境空间相互作用的关键因素。在这方面，生物力学刺激可以引发显著的生理级联反应，从而可能调节毒性。脱氧雪腐镰刀菌烯醇（DON，呕吐毒素）是镰刀菌属产生的最常见的霉菌毒素之一，它被用来探索 A431 细胞中生物力学刺激和细胞毒性之间的微妙相互作用。事实上，除了作为食物污染物之外，DON 还是几种器官系统的相关毒素。生物力学刺激和霉菌毒素的结合揭示了 DON 如何在浓度甚至低于常规毒性研究中已知的细胞毒性浓度下，损害影响细胞形态、微管蛋白和溶酶体的关键功能。亚毒性浓度的 DON（0.1-1 μM）损害了 A431 细胞对生物力学刺激的反应能力，而这种刺激通常在这些细胞中维持营养作用。此外，DON（0.1-10 μM）的作用部分被单轴拉伸（0.5 Hz，24 h，15%变形）所调节。最终，蛋白质组学分析显示 DON 有潜力改变几种对于细胞黏附和细胞骨架调节至关重要的蛋白质，这表明生物力学和霉菌毒素的细胞毒性潜力之间存在分子联系。
