Li Guoliang, Wang Kaidong, Zuo Kai, Shi Ge, Cai Qian, Huang Min
School of Public Health and Management, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
School of Public Health and Management, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
Ecotoxicol Environ Saf. 2023 Apr 15;255:114780. doi: 10.1016/j.ecoenv.2023.114780. Epub 2023 Mar 16.
Atrazine (ATR) is one of the herbicides widely used worldwide. Meanwhile, it is an environmental endocrine disruptor that can cross the blood-brain barrier and cause damage to the endocrine-nervous system, especially by affecting the normal secretion of dopamine (DA). Regrettably, effector markers and cascade response mechanisms in damaged dopaminergic neurons induced by ATR exposure remain elusive. In this paper, we focus on investigating aggregation and position change of transactive response DNA-binding protein-43 (TDP-43) after ATR exposure, and illustrating whether TDP-43 can serve as a potential marker of mitochondrial dysfunction which causes damage to dopaminergic neurons. In our study, we used rat adrenal pheochromocytoma cell line 12 (PC12) to establish an in vitro model of dopaminergic neurons. After PC12 was intervened by ATR, we found reduced DA cycling and DA levels, and that TDP-43 aggregated continuously in the cytoplasm and then translocated to mitochondria. Furthermore, the studies we have performed showed that the translocation can cause mitochondrial dysfunction through activating the unfolded mitochondrial protein response (UPRmt), ultimately causing damage to dopaminergic neuron. The research we have done suggests that TDP-43 can serve as a potential effector marker of dopaminergic neuron damaged caused by ATR exposure.
阿特拉津（ATR）是全球广泛使用的除草剂之一。同时，它是一种环境内分泌干扰物，能够穿过血脑屏障并对内分泌神经系统造成损害，尤其是通过影响多巴胺（DA）的正常分泌。遗憾的是，ATR暴露诱导的受损多巴胺能神经元中的效应标志物和级联反应机制仍不清楚。在本文中，我们着重研究ATR暴露后反式作用应答DNA结合蛋白43（TDP-43）的聚集和位置变化，并阐明TDP-43是否可作为导致多巴胺能神经元损伤的线粒体功能障碍的潜在标志物。在我们的研究中，我们使用大鼠肾上腺嗜铬细胞瘤细胞系12（PC12）建立多巴胺能神经元的体外模型。PC12经ATR干预后，我们发现DA循环和DA水平降低，并且TDP-43在细胞质中持续聚集，然后转移至线粒体。此外，我们进行的研究表明，这种转移可通过激活未折叠线粒体蛋白反应（UPRmt）导致线粒体功能障碍，最终对多巴胺能神经元造成损伤。我们所做的研究表明，TDP-43可作为ATR暴露导致的多巴胺能神经元损伤的潜在效应标志物。
