'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.
'Systems toxicology' approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.
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DOI：
10.1186/1741-7007-6-25
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发表时间：
2008-06-03
期刊：
影响因子：
5.4
通讯作者：
Kille, Peter
中科院分区：
文献类型：
--
作者：
Bundy, Jacob G.;Sidhu, Jasmin K.;Rana, Faisal;Spurgeon, David J.;Svendsen, Claus;Wren, Jodie F.;Sturzenbaum, Stephen R.;Morgan, A. John;Kille, Peter
需要新的方法来研究非模式生物，以监测分子和功能生物水平上的毒性破坏的影响。我们将蚯蚓暴露于亚致死水平的铜（10-480 mg/kg土壤）中70天，并监测分子（cDNA转录物微阵列和基于核磁共振的代谢谱：代谢组学）和生态/功能终点（繁殖率和体重变化，与种群水平的影响直接相关）。这两个分子终点，代谢组学和转录组学，是高度敏感的，具有明确的铜诱导的差异，即使在低于那些导致生殖参数降低的水平。微阵列和代谢组学数据提供的证据表明，铜暴露导致能量代谢的破坏：氧化磷酸化酶的转录物显着过度代表，碳水化合物代谢酶（麦芽糖酶-葡糖淀粉酶，甘露糖苷酶）的转录物的增加相应地减少了小分子代谢物（葡萄糖，甘露糖）。将酶和代谢物作为功能性队列进行处理，可以明确推断能量代谢（碳水化合物使用和氧化磷酸化）的变化，而采用“生物标志物”方法进行数据分析是不可能的。多个后基因组技术可以结合起来，提供有关化学污染物的毒性作用的机制信息，即使是非模式生物与一些额外的机制毒理学数据。代谢组学和微阵列图谱的70天无明显影响和最低可观察影响浓度（NOEC和LOEC）分别为10和40 mg kg-1，表明铜在生态和功能相关水平上干扰重要土壤生物的能量代谢。
New methods are needed for research into non-model organisms, to monitor the effects of toxic disruption at both the molecular and functional organism level. We exposed earthworms (Lumbricus rubellus Hoffmeister) to sub-lethal levels of copper (10–480 mg/kg soil) for 70 days as a real-world situation, and monitored both molecular (cDNA transcript microarrays and nuclear magnetic resonance-based metabolic profiling: metabolomics) and ecological/functional endpoints (reproduction rate and weight change, which have direct relevance to population-level impacts). Both of the molecular endpoints, metabolomics and transcriptomics, were highly sensitive, with clear copper-induced differences even at levels below those that caused a reduction in reproductive parameters. The microarray and metabolomic data provided evidence that the copper exposure led to a disruption of energy metabolism: transcripts of enzymes from oxidative phosphorylation were significantly over-represented, and increases in transcripts of carbohydrate metabolising enzymes (maltase-glucoamylase, mannosidase) had corresponding decreases in small-molecule metabolites (glucose, mannose). Treating both enzymes and metabolites as functional cohorts led to clear inferences about changes in energetic metabolism (carbohydrate use and oxidative phosphorylation), which would not have been possible by taking a 'biomarker' approach to data analysis. Multiple post-genomic techniques can be combined to provide mechanistic information about the toxic effects of chemical contaminants, even for non-model organisms with few additional mechanistic toxicological data. With 70-day no-observed-effect and lowest-observed-effect concentrations (NOEC and LOEC) of 10 and 40 mg kg-1 for metabolomic and microarray profiles, copper is shown to interfere with energy metabolism in an important soil organism at an ecologically and functionally relevant level.
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