Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
School of Public Health, Southeast University, Nanjing 210009, China.
Environ Sci Technol. 2023 Mar 28;57(12):4940-4950. doi: 10.1021/acs.est.2c08644. Epub 2023 Mar 13.
6-PPD quinone (6-PPDQ) can be transformed from 6-PPD through ozonation. Nevertheless, the potential neurotoxicity of 6-PPDQ after long-term exposure and the underlying mechanism are largely unclear. In , we here observed that 0.1-10 μg/L of 6-PPDQ caused several forms of abnormal locomotion behaviors. Meanwhile, the neurodegeneration of D-type motor neurons was observed in 10 μg/L of 6-PPDQ-exposed nematodes. The observed neurodegeneration was associated with the activation of the Ca channel DEG-3-mediated signaling cascade. In this signaling cascade, expressions of , , , , , and were increased by 10 μg/L of 6-PPDQ. Moreover, among genes encoding neuronal signals required for the control of stress response, expressions of and were decreased by 0.1-10 μg/L of 6-PPDQ, and expressions of and were decreased by 10 μg/L of 6-PPDQ. RNAi of , , , and resulted in the susceptibility to 6-PPDQ toxicity in decreasing locomotory ability and in inducing neurodegeneration, suggesting that JNK-1, DBL-1, DAF-7, and GLB-10 were also required for the induction of 6-PPDQ neurotoxicity. Molecular docking analysis further demonstrated the binding potential of 6-PPDQ to DEG-3, JNK-1, DBL-1, DAF-7, and GLB-10. Together, our data suggested the exposure risk of 6-PPDQ at environmentally relevant concentrations in causing neurotoxicity in organisms.
6-PPD 醌（6-PPDQ）可以通过臭氧化作用从 6-PPD 转化而来。然而，6-PPDQ 长期暴露后的潜在神经毒性及其潜在机制在很大程度上尚不清楚。在本文中，我们观察到 0.1-10μg/L 的 6-PPDQ 会引起几种形式的异常运动行为。同时，在 10μg/L 的 6-PPDQ 暴露的线虫中观察到 D 型运动神经元的神经退行性变。观察到的神经退行性变与钙通道 DEG-3 介导的信号级联的激活有关。在这个信号级联中，0.1-10μg/L 的 6-PPDQ 会增加 、 、 、 、和 的表达。此外，在编码控制应激反应所需的神经元信号的基因中，0.1-10μg/L 的 6-PPDQ 会降低 和 的表达，而 10μg/L 的 6-PPDQ 会降低 和 的表达。 、 、 、和 的 RNAi 导致运动能力下降和神经退行性变易感性增加，这表明 JNK-1、DBL-1、DAF-7 和 GLB-10 也需要诱导 6-PPDQ 神经毒性。分子对接分析进一步证明了 6-PPDQ 与 DEG-3、JNK-1、DBL-1、DAF-7 和 GLB-10 的结合潜力。总之，我们的数据表明，在环境相关浓度下暴露于 6-PPDQ 会增加生物体产生神经毒性的风险。
