Aschner M, Palinski C, Sperling M, Karst U, Schwerdtle T, Bornhorst J
Department of Molecular Pharmacology, Neuroscience, and Pediatrics, Albert Einstein College of Medicine, Bronx NY, USA.
Metallomics. 2017 Apr 19;9(4):357-364. doi: 10.1039/c6mt00265j.
Systemic trafficking and storage of essential metal ions play fundamental roles in living organisms by serving as essential cofactors in various cellular processes. Thereby metal quantification and localization are critical steps in understanding metal homeostasis, and how their dyshomeostasis might contribute to disease etiology and the ensuing pathologies. Furthermore, the amount and distribution of metals in organisms can provide insight into their underlying mechanisms of toxicity and toxicokinetics. While in vivo studies on metal imaging in mammalian experimental animals are complex, time- and resource-consuming, the nematode Caenorhabditis elegans (C. elegans) provides a suitable comparative and complementary model system. Expressing homologous genes to those inherent to mammals, including those that regulate metal homeostasis and transport, C. elegans has become a powerful tool to study metal homeostasis and toxicity. A number of recent technical advances have been made in the development and application of analytical methods to visualize metal ions in C. elegans. Here, we briefly summarize key findings and challenges of the three main techniques and their application to the nematode, namely sensing fluorophores, microbeam synchrotron radiation X-ray fluorescence as well as laser ablation (LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS).
必需金属离子的全身运输和储存通过在各种细胞过程中作为必需辅因子,在生物体中发挥着基本作用。因此,金属定量和定位是理解金属稳态以及其稳态失调如何导致疾病病因和后续病理的关键步骤。此外,生物体中金属的含量和分布可以为其潜在的毒性机制和毒物动力学提供见解。虽然在哺乳动物实验动物中进行金属成像的体内研究复杂、耗时且耗费资源,但线虫秀丽隐杆线虫(C. elegans)提供了一个合适的比较和互补模型系统。秀丽隐杆线虫表达与哺乳动物固有基因同源的基因,包括那些调节金属稳态和运输的基因,已成为研究金属稳态和毒性的有力工具。在用于可视化秀丽隐杆线虫中金属离子的分析方法的开发和应用方面,最近取得了一些技术进展。在这里,我们简要总结三种主要技术的关键发现和挑战及其在线虫中的应用,即传感荧光团、微束同步辐射X射线荧光以及与电感耦合等离子体质谱(ICP-MS)联用的激光烧蚀(LA)。