Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, 210009, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, 210009, China; Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen, 518122, China; College of Biology and Food Engineering, Chongqing Three Gorges University, Wanzhou, 404100, China.
Chemosphere. 2021 May;271:129589. doi: 10.1016/j.chemosphere.2021.129589. Epub 2021 Jan 8.
The epigenetic regulation mechanisms for toxicity induction of nanoplastics in organisms remain largely unknown. In Caenorhabditis elegans, we found that prolonged exposure to 1-100 μg/L polystyrene nanoparticles (PS-NPs) decreased expression of MET-2, a H3K9 methyltransferase. Meanwhile, RNAi knockdown of met-2 suppressed the PS-NPs toxicity in inducing production of reactive oxygen species (ROS) and in decreasing locomotion behavior, which suggesting that the decrease in MET-2 expression reflected a protective response. This resistance to PS-NPs toxicity could be further detected in worms with met-2 RNAi knockdown in both intestinal cells and germline cells. In PS-NPs exposed worms, intestinal RNAi knockdown of met-2 significantly increased expressions of daf-16, bar-1, and elt-2. Intestinal RNAi knockdown of daf-16, bar-1, or elt-2 suppressed the resistance of met-2(RNAi) worms to PS-NPs toxicity, suggesting that MET-2 functioned upstream of ELT-2, BAR-1, and DAF-16 in intestinal cells to control PS-NPs toxicity. Moreover, in PS-NPs exposed worms, germline RNAi knockdown of met-2 significantly decreased expressions of wrt-3 and pat-12. RNAi knockdown of wrt-3 or pat-12 further inhibited the susceptibility of worms overexpressing germline MET-2 to PS-NPs toxicity, suggesting that MET-2 functioned upstream of PAT-12 and WRT-3 in germline cells to control PS-NPs toxicity. Therefore, our data provided an important molecular basis for MET-2-mediated methylation regulation in causing protective response to nanoplastics in organisms.
纳米塑料在生物体中诱导毒性的表观遗传调控机制在很大程度上尚不清楚。在秀丽隐杆线虫中，我们发现，长时间暴露于 1-100μg/L 的聚苯乙烯纳米颗粒（PS-NPs）会降低 H3K9 甲基转移酶 MET-2 的表达。同时，met-2 的 RNAi 敲低抑制了 PS-NPs 诱导活性氧（ROS）产生和运动行为减少的毒性，这表明 MET-2 表达的降低反映了一种保护反应。这种对 PS-NPs 毒性的抗性可以在具有 met-2 RNAi 敲低的线虫中进一步检测到，无论是在肠细胞还是生殖细胞中。在暴露于 PS-NPs 的线虫中，met-2 的肠道 RNAi 敲低显著增加了 daf-16、bar-1 和 elt-2 的表达。肠道 RNAi 敲低 daf-16、bar-1 或 elt-2 抑制了 met-2(RNAi)线虫对 PS-NPs 毒性的抗性，表明 MET-2 在肠细胞中在上游作用于 ELT-2、BAR-1 和 DAF-16 以控制 PS-NPs 毒性。此外，在暴露于 PS-NPs 的线虫中，met-2 的生殖系 RNAi 敲低显著降低了 wrt-3 和 pat-12 的表达。wrt-3 或 pat-12 的 RNAi 敲低进一步抑制了过度表达生殖系 MET-2 的线虫对 PS-NPs 毒性的敏感性，表明 MET-2 在生殖系细胞中在上游作用于 PAT-12 和 WRT-3 以控制 PS-NPs 毒性。因此，我们的数据为 MET-2 介导的甲基化调节在生物体中对纳米塑料产生保护反应提供了重要的分子基础。
