Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119 Wuppertal, Germany.
TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena-Wuppertal, 14558 Nuthetal, Germany.
Int J Mol Sci. 2022 Sep 15;23(18):10748. doi: 10.3390/ijms231810748.
Manganese (Mn) is an essential ubiquitous transition metal and, when occupationally or environmentally overexposed, a well-known risk factor for several neurological pathologies. However, the molecular mechanisms underlying Mn-induced neurotoxicity are largely unknown. In this study, addressing RNA-Seq analysis, bioavailability and survival assays, key pathways of transcriptional responses to Mn overexposure were investigated in the model organism (), providing insights into the Mn-induced cellular stress and damage response. Comparative transcriptome analyses identified a large number of differentially expressed genes (DEGs) in nematodes exposed to MnCl, and functional annotation suggested oxidative nucleotide damage, unfolded protein response and innate immunity as major damage response pathways. Additionally, a time-dependent increase in the transcriptional response after MnCl exposure was identified by means of increased numbers of DEGs, indicating a time-dependent response and activation of the stress responses in Mn neurotoxicity. The data provided here represent a powerful transcriptomic resource in the field of Mn toxicity, and therefore, this study provides a useful basis for further planning of targeted mechanistic studies of Mn-induced neurotoxicity that are urgently needed in the face of increasing industrially caused environmental pollution with Mn.
锰(Mn)是一种必需的普遍存在的过渡金属,当职业性或环境性暴露过度时,是几种神经病理学的已知危险因素。然而,锰诱导的神经毒性的分子机制在很大程度上尚不清楚。在这项研究中,通过 RNA-Seq 分析、生物利用度和存活测定,研究了模型生物(秀丽隐杆线虫)中对 Mn 过度暴露的转录反应的关键途径,深入了解了 Mn 诱导的细胞应激和损伤反应。比较转录组分析鉴定了暴露于 MnCl2 的线虫中大量差异表达基因(DEGs),功能注释表明氧化核苷酸损伤、未折叠蛋白反应和先天免疫是主要的损伤反应途径。此外,通过增加 DEGs 的数量,鉴定出 MnCl2 暴露后转录反应的时间依赖性增加,表明 Mn 神经毒性中的应激反应具有时间依赖性和激活。这里提供的数据代表了 Mn 毒性领域的强大转录组资源,因此,本研究为进一步计划针对 Mn 诱导的神经毒性的有针对性的机制研究提供了有用的基础,这在面对日益增加的工业造成的 Mn 环境污染时是迫切需要的。