College of Life Sciences, Nanjing Agricultural University, Nanjing, China.
Medical School, Southeast University, Nanjing, China.
Chemosphere. 2023 Mar;318:137986. doi: 10.1016/j.chemosphere.2023.137986. Epub 2023 Jan 27.
Multi-walled carbon nanotube (MWCNT), a kind of carbon-based nanomaterials, has been extensively utilized in a variety of fields. In Caenorhabditis elegans, MWCNT exposure can result in toxicity not only at parental generation (P0-G) but also in the offspring. However, the underlying mechanisms remain still largely unknown. DAF-12, a transcriptional factor (TF), was previously found to be activated and involved in transgenerational toxicity control after MWCNT exposure. In this study, we observed that exposure to 0.1-10 μg/L MWCNTs caused the significant decrease in expression of tbh-1 encoding a tyramine beta-hydroxylase with the function to govern the octopamine synthesis, suggesting the inhibition in octopamine signal. After exposure to 0.1 μg/L MWCNT, the decrease in tbh-1 expression could be also detected in F1-G and F2-G. Moreover, in germline cells, the TF DAF-12 regulated transgenerational MWCNT toxicity by suppressing expression and function of TBH-1. Meanwhile, exposure to 0.1-10 μg/L MWCNTs induced the increase in octr-1 expression and the decrease in ser-6 expression. After exposure to 0.1 μg/L MWCNT, the increased octr-1 expression and the decreased ser-6 expression were further observed in F1-G and F2-G. Germline TBH-1 controlled transgenerational MWCNT toxicity by regulating the activity of octopamine receptors (SER-6 and OCTR-1) in offspring. Furthermore, in the offspring, SER-6 and OCTR-1 affected the induction of MWCNT toxicity by upregulating or downregulating the level of ELT-2, a GATA TF. Taken together, these findings suggested possible link between alteration in octopamine related signals and MWCNT toxicity induction in offspring in organisms.
多壁碳纳米管 (MWCNT) 作为一种碳基纳米材料，已被广泛应用于多个领域。在秀丽隐杆线虫中，MWCNT 暴露不仅在亲代世代 (P0-G) ，而且在子代中都会导致毒性。然而，其潜在机制在很大程度上仍然未知。先前发现转录因子 (TF) DAF-12 在暴露于 MWCNT 后被激活并参与跨代毒性控制。在这项研究中，我们观察到，暴露于 0.1-10μg/L MWCNTs 会导致编码 tyramine beta-hydroxylase 的 tbh-1 表达显著下降，该酶的功能是调节章鱼胺的合成，表明章鱼胺信号受到抑制。暴露于 0.1μg/L MWCNT 后，还可以在 F1-G 和 F2-G 中检测到 tbh-1 表达的下降。此外，在生殖细胞中，TF DAF-12 通过抑制 TBH-1 的表达和功能来调节跨代 MWCNT 毒性。同时，暴露于 0.1-10μg/L MWCNTs 会诱导 octr-1 表达增加和 ser-6 表达减少。暴露于 0.1μg/L MWCNT 后，还可以在 F1-G 和 F2-G 中观察到 octr-1 表达增加和 ser-6 表达减少。生殖细胞 TBH-1 通过调节子代章鱼胺受体 (SER-6 和 OCTR-1) 的活性来控制跨代 MWCNT 毒性。此外，在子代中，SER-6 和 OCTR-1 通过上调或下调 GATA TF ELT-2 的水平来影响 MWCNT 毒性的诱导。综上所述，这些发现表明在生物体中，章鱼胺相关信号的改变与 MWCNT 毒性诱导之间可能存在联系。
