Pallares Roger M, An Dahlia D, Hébert Solène, Faulkner David, Loguinov Alex, Proctor Michael, Villalobos Jonathan A, Bjornstad Kathleen A, Rosen Chris J, Vulpe Christopher, Abergel Rebecca J
Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Metallomics. 2021 Dec 6;13(12). doi: 10.1093/mtomcs/mfab061.
Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.
铕是一种在光电子学中具有很高价值的镧系金属。尽管铕被用于许多商业产品中，但其毒理学特征仅得到部分表征，大多数研究集中于确定不同系统中的致死剂量或体内生物累积情况。本文描述了一项在酿酒酵母中进行的铕全基因组毒理基因组学研究，酿酒酵母与人类具有许多共同的生物学功能。通过使用多维方法以及功能和网络分析，我们确定了一组与酵母缓解金属毒性反应相关的基因和蛋白质，其中包括通过囊泡介导运输的金属排出途径、调节生物相关阳离子的途径以及减轻金属诱导应激的过程。此外，分析表明铕通过破坏具有金属结合位点的伴侣蛋白和共伴侣蛋白的功能来促进酵母毒性。我们研究中突出的几个基因和蛋白质在人类中有直系同源物，这表明它们可能参与了铕对人类的毒性作用。通过确定铕的内源性靶点以及现有的可降低其毒性的途径，我们可以确定可能有助于制定未来治疗策略的特定基因和蛋白质。
