College of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, China.
Medical School, Southeast University, Nanjing, 210009, China.
Chemosphere. 2022 Dec;308(Pt 1):136154. doi: 10.1016/j.chemosphere.2022.136154. Epub 2022 Aug 24.
The mitochondrial unfolded protein response (mt UPR) is important for organisms against the toxicity from toxicants and stresses. Polystyrene nanoparticle (PS-NP), one of the emerging pollutants, has aroused increasing concern for its toxicity in the offspring. Nevertheless, the molecular basis for this transgenerational toxicity remains largely unclear. In this study, the role of mt UPR in the induction of transgenerational toxicity was determined in Caenorhabditis elegans (C. elegans) after parental exposure to PS-NP. After exposure to PS-NP (1-100 μg/L), the suppression in mt UPR showed the concentration-dependent in nematodes from P0 generation (P0-G) to F2-G. Moreover, the decreased expression of genes required for controlling mt UPR (atfs-1, dve-1, and ubl-5 genes) were observed from P0-G to F2-G after exposure to PS-NP (1 μg/L). The adverse effects on locomotion and reproductive capacity were more severe over generations in nematodes with RNAi of these three genes, indicating that these genes were involved in controlling transgenerational toxicity. After parental PS-NP exposure (1 μg/L), the mt UPR was significantly inhibited by RNAi of atfs-1, dve-1, and ubl-5, indicating the association between the transgenerational PS-NP toxicity and mt UPR suppression. Additionally, during the transgenerational process, RNAi of atfs-1, dve-1, and ubl-5 enhanced the PS-NP toxicity by suppressing mt UPR, while RNAi of daf-2 encoding an insulin receptor inhibited the PS-NP toxicity by increasing mt UPR. Therefore, our data highlighted the role of inhibition in mt UPR in mediating the transgenerational nanoplastic toxicity in nematodes.
线粒体未折叠蛋白反应（mt UPR）对于生物体抵抗毒物和应激的毒性非常重要。聚苯乙烯纳米颗粒（PS-NP）作为一种新兴污染物，其毒性引起了越来越多的关注。然而，这种跨代毒性的分子基础在很大程度上仍不清楚。在这项研究中，通过在亲代暴露于 PS-NP 后，在秀丽隐杆线虫（C. elegans）中确定了 mt UPR 在诱导跨代毒性中的作用。暴露于 PS-NP（1-100μg/L）后，P0 代（P0-G）到 F2-G 的线虫 mt UPR 抑制呈浓度依赖性。此外，暴露于 PS-NP（1μg/L）后，从 P0-G 到 F2-G 观察到控制 mt UPR 的基因（atfs-1、dve-1 和 ubl-5 基因）的表达减少。这些基因的 RNAi 会导致线虫的运动和生殖能力在几代中受到更严重的影响，表明这些基因参与控制跨代毒性。在亲代 PS-NP 暴露（1μg/L）后，atfs-1、dve-1 和 ubl-5 的 RNAi 显著抑制了 mt UPR，表明跨代 PS-NP 毒性与 mt UPR 抑制之间存在关联。此外，在跨代过程中，atfs-1、dve-1 和 ubl-5 的 RNAi 通过抑制 mt UPR 增强了 PS-NP 的毒性，而胰岛素受体编码基因 daf-2 的 RNAi 通过增加 mt UPR 抑制了 PS-NP 的毒性。因此，我们的数据强调了抑制 mt UPR 在介导线虫中跨代纳米塑料毒性中的作用。
