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玉米赤霉烯酮通过 DRP-1 介导线粒体片段化和凋亡诱导帕金森病模型中的多巴胺能神经退行性变。

Zearalenone Induces Dopaminergic Neurodegeneration via DRP-1-Involved Mitochondrial Fragmentation and Apoptosis in a Parkinson's Disease Model.

机构信息

Institute of Food Safety and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan.

Department of Public Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan.

出版信息

J Agric Food Chem. 2021 Oct 13;69(40):12030-12038. doi: 10.1021/acs.jafc.1c05836. Epub 2021 Sep 29.

DOI:10.1021/acs.jafc.1c05836
PMID:34586801
Abstract

The contamination of mycotoxin zearalenone (ZEN) in foods has been reported worldwide, resulting in potential risks to food safety. However, the toxic mechanism of ZEN on neurodegenerative diseases has not been fully elucidated. Therefore, this study conducted ZEN neurotoxicity assessment on Parkinson's disease (PD)-related dopaminergic neurodegeneration and mitochondrial dysfunction using . The results demonstrated that dopaminergic neuron damage was induced by ZEN exposure (1.25, 10, and 50 μM), and dopaminergic neuron-related behaviors were adversely affected subsequently. Additionally, the mitochondrial fragmentation was significantly increased by ZEN exposure. Moreover, upregulated expression of mitochondrial fission and cell apoptosis-related genes (, , , and ) revealed the crucial role of DRP-1 on ZEN-induced neurotoxicity, which was further confirmed by mutant and RNAi assays. In conclusion, our study indicates ZEN-induced dopaminergic neurodegeneration DRP-1-involved mitochondrial fragmentation and apoptosis, which might cause harmful effects on PD-related symptoms.

摘要

真菌毒素玉米赤霉烯酮(ZEN)在食品中的污染已在全球范围内得到报道,这可能对食品安全造成潜在风险。然而,ZEN 对神经退行性疾病的毒性机制尚未完全阐明。因此,本研究采用. 对帕金森病(PD)相关的多巴胺能神经退行性变和线粒体功能障碍进行 ZEN 神经毒性评估。结果表明,ZEN 暴露(1.25、10 和 50 μM)会诱导多巴胺能神经元损伤,随后会对多巴胺能神经元相关行为产生不利影响。此外,ZEN 暴露会显著增加线粒体片段化。此外,上调表达的线粒体分裂和细胞凋亡相关基因(、、、和 )表明 DRP-1 在 ZEN 诱导的神经毒性中起着关键作用,这通过 突变体和 RNAi 实验进一步得到证实。总之,本研究表明 ZEN 诱导的多巴胺能神经退行性变涉及 DRP-1 介导的线粒体分裂和凋亡,这可能对 PD 相关症状产生有害影响。

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