College of Public Health, Shantou University, Shantou, 515063, Guangdong Province, China.
College of Public Health, Shantou University, Shantou, 515063, Guangdong Province, China; Department of Toxicology, College of Public Health, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
Environ Pollut. 2024 Jan 1;340(Pt 1):122811. doi: 10.1016/j.envpol.2023.122811. Epub 2023 Oct 25.
Atrazine (ATR) is a widely used agricultural herbicide, and its accumulation in soil and water can cause various environmental health problems. ATR has neurotoxic effects on dopaminergic neurons, which can lead to a Parkinson's disease (PD)-like syndrome. Epigenetics regulates gene expression dynamically through DNA methylation, histone post-translational modification, microRNA (miRNA) interaction, and RNA methylation. MicroRNA (miRNA), representing one of the primary epigenetic mechanisms responsible for regulating gene expression, plays a crucial role in maintaining normal cellular function, while dysregulation of miRNA expression has been observed in PD. This study aims to investigate the regulatory mechanisms of miRNA in ATR exposure. The results show that ATR-exposure significantly upregulates the expression level of miR-217-5p. Both miR-217-5p overexpression and ATR exposure is able to trigger the autophagy process and apoptosis. Conversely, inhibiting the expression of miR-217-5p can reverse the levels of ATR-induced autophagy and apoptosis. Moreover, ATR causes damage to dopaminergic neurons, as indicated by the altered expression of tyrosine hydroxylase and α-synuclein. Taken together, these results suggest that ATR-induced autophagy can accelerate the progression of neurodegenerative diseases and that miR-217-5p is probably an important target involved in ATR-induced dopaminergic damage, shedding important light on the development of a novel strategy for treating neurodegenerative diseases.
莠去津（ATR）是一种广泛使用的农业除草剂，其在土壤和水中的积累会导致各种环境健康问题。ATR 对多巴胺能神经元具有神经毒性作用，这可能导致帕金森病（PD）样综合征。表观遗传学通过 DNA 甲基化、组蛋白翻译后修饰、microRNA（miRNA）相互作用和 RNA 甲基化来动态调节基因表达。miRNA 作为主要的表观遗传机制之一，代表负责调节基因表达的主要机制之一，在维持正常细胞功能方面起着至关重要的作用，而 miRNA 表达的失调已在 PD 中观察到。本研究旨在探讨 miRNA 在 ATR 暴露中的调控机制。结果表明，ATR 暴露显著上调了 miR-217-5p 的表达水平。miR-217-5p 的过表达和 ATR 暴露都能触发自噬过程和细胞凋亡。相反，抑制 miR-217-5p 的表达可以逆转 ATR 诱导的自噬和细胞凋亡水平。此外，ATR 导致多巴胺能神经元损伤，酪氨酸羟化酶和α-突触核蛋白的表达改变表明了这一点。综上所述，这些结果表明 ATR 诱导的自噬可能会加速神经退行性疾病的进展，而 miR-217-5p 可能是 ATR 诱导的多巴胺能损伤中涉及的重要靶标之一，为治疗神经退行性疾病的新策略的发展提供了重要线索。
