Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf, Switzerland.
Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3490-5. doi: 10.1073/pnas.1319388111. Epub 2014 Feb 18.
Understanding mechanistic and cellular events underlying a toxicological outcome allows the prediction of impact of environmental stressors to organisms living in different habitats. A systems-based approach aids in characterizing molecular events, and thereby the cellular pathways that have been perturbed. However, mapping only adverse outcomes of a toxicant falls short of describing the stress or adaptive response that is mounted to maintain homeostasis on perturbations and may confer resistance to the toxic insult. Silver is a potential threat to aquatic organisms because of the increasing use of silver-based nanomaterials, which release free silver ions. The effects of silver were investigated at the transcriptome, proteome, and cellular levels of Chlamydomonas reinhardtii. The cells instigate a fast transcriptome and proteome response, including perturbations in copper transport system and detoxification mechanisms. Silver causes an initial toxic insult, which leads to a plummeting of ATP and photosynthesis and damage because of oxidative stress. In response, the cells mount a defense response to combat oxidative stress and to eliminate silver via efflux transporters. From the analysis of the perturbations of the cell's functions, we derived a detailed mechanistic understanding of temporal dynamics of toxicity and adaptive response pathways for C. reinhardtii exposed to silver.
了解毒理学结果背后的机制和细胞事件,可以预测生活在不同生境中的生物体受环境胁迫的影响。基于系统的方法有助于描述分子事件,并阐明受到干扰的细胞途径。然而,仅描述毒物的不良后果并不能描述为了维持体内平衡而产生的应激或适应性反应,也不能赋予对毒物侵害的抗性。由于越来越多地使用释放游离银离子的银基纳米材料,银对水生生物构成了潜在威胁。本研究在莱茵衣藻的转录组、蛋白质组和细胞水平上研究了银的作用。细胞引发了快速的转录组和蛋白质组反应,包括铜转运系统和解毒机制的干扰。银会造成初始的毒性损伤,导致 ATP 和光合作用急剧下降,并因氧化应激而受损。作为回应,细胞会启动防御反应来对抗氧化应激,并通过外排转运蛋白来消除银。通过对细胞功能的干扰进行分析,我们对莱茵衣藻暴露于银时的毒性和适应性反应途径的时间动态得出了详细的机制理解。