Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
J Hazard Mater. 2024 Mar 5;465:133345. doi: 10.1016/j.jhazmat.2023.133345. Epub 2023 Dec 22.
Increasingly copper pollution in the environment exacerbates the risk of neurodegenerative diseases. It is necessary to look for effective targets and safe methods for protecting from copper-induced neurotoxicity. Here we firstly explored the impact of copper-exposure on expression profiles in zebrafish. Copper reduced embryo hatching, increased mortality and caused embryonic developmental abnormalities and behavioral dysfunction in juveniles. Transcriptomic analysis revealed that differential genes related to neuron were highly associated with oxidative stress especially enriched to FoxO pathway. Through further validation in Caenorhabditis elegans, copper resulted in nematode neurodegenerative movement disorders and neuronal damage, along with increased levels of reactive oxygen species (ROS) as well as decreased expressions of antioxidant-related enzymes and downstream genes which was also involved in FoxO signaling pathway. Bacillus smithii XY1, a novel strain with an excellent antioxidative activity, showed a great alleviative effect on copper-induced neurotoxicity that was related to FoxO stimulation, being a potential candidate for copper pollution management. Overall, these results suggested that FoxO pathway activation can regard as a strategy for mitigating neurotoxicity caused by copper and B. smithii XY1 with excellent tolerance and outstanding antioxidation specially targeted for FoxO has a promising application in controlling copper contamination.
环境中铜污染的增加加剧了神经退行性疾病的风险。有必要寻找有效的靶点和安全的方法来防止铜诱导的神经毒性。在这里，我们首先探索了铜暴露对斑马鱼表达谱的影响。铜暴露降低了胚胎孵化率，增加了死亡率，并导致幼鱼出现胚胎发育异常和行为功能障碍。转录组分析显示，与神经元相关的差异基因与氧化应激高度相关，特别是与 FoxO 途径富集。通过在秀丽隐杆线虫中的进一步验证，铜导致线虫神经退行性运动障碍和神经元损伤，同时增加活性氧 (ROS) 水平，降低抗氧化相关酶和下游基因的表达，这些基因也参与 FoxO 信号通路。具有优异抗氧化活性的新型菌株 Bacillus smithii XY1 对铜诱导的神经毒性具有显著的缓解作用，这与 FoxO 刺激有关，是铜污染治理的潜在候选菌株。总的来说，这些结果表明 FoxO 通路的激活可以作为减轻铜引起的神经毒性的一种策略，而具有优异耐受性和针对 FoxO 的卓越抗氧化特性的 B. smithii XY1 在控制铜污染方面具有广阔的应用前景。
