Mechanism of miR-143 regulating ERK5 signaling pathway-mediated manganese-induced striatal neuronal apoptosis

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-05-14 DOI:10.1016/j.ecoenv.2025.118266

Huan Mao , Yidan Wei , Cheng Liu , Jianmin Yang , Liyu Su , Yuyan Cen , Feng Wang , Deyu Zhu , Yu Deng , Yan Li

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引用次数: 0

Abstract

Overexposure manganese can induce neurotoxicity and apoptosis, in addition, miRNAs are widely involved in the apoptotic process of neurons. Therefore, it is crucial to explore the mechanism of miRNAs in manganese-induced neuronal apoptosis and then to find potential targets. Our present study showed that miR-143 expression was increased in striatum after exposure high doses of manganese. Then, we upregulated miR-143 expression via stereotaxic, and overexpression of miR-143 promoted apoptosis in striatal neurons. Further studies showed a negative regulatory relationship between miR-143 and ERK5, miR-143 upregulation decreased ERK5 mRNA level, inhibiting ERK5 signaling pathway, increasing the expression of Bax and Caspase-3, and exacerbating the apoptosis of striatal neurons. In conclusion, these results suggest that overexpression of miR-143 inhibited the ERK5 signaling pathway and promoted manganese-induced apoptosis in striatal neurons.

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miR-143调控ERK5信号通路介导的锰诱导纹状体神经元凋亡的机制

过量暴露于锰可引起神经毒性和细胞凋亡，并且mirna广泛参与神经元的凋亡过程。因此，探索mirna在锰诱导神经元凋亡中的作用机制并寻找潜在靶点至关重要。我们目前的研究表明，暴露于高剂量锰后，纹状体中miR-143的表达增加。然后，我们通过立体定向上调miR-143的表达，miR-143的过表达促进纹状体神经元的凋亡。进一步研究发现miR-143与ERK5存在负调控关系，miR-143上调降低ERK5 mRNA水平，抑制ERK5信号通路，增加Bax和Caspase-3的表达，加剧纹状体神经元的凋亡。综上所述，这些结果表明miR-143过表达抑制ERK5信号通路，促进锰诱导的纹状体神经元凋亡。

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.