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中华临床实验室管理电子杂志 ›› 2023, Vol. 11 ›› Issue (02) : 71 -78. doi: 10.3877/cma.j.issn.2095-5820.2023.02.002

论著

鱼藤酮通过降低线粒体钙离子单向转运体蛋白表达促进多巴胺能神经元铁死亡
谢艾伦, 郑冬燕, 蔡紫薇, 卢仁建, 彭永明, 张贺(), 陈家隆()   
  1. 523808 广东东莞,广东医科大学公共卫生学院预防医学系
  • 收稿日期:2022-11-06 出版日期:2023-05-28
  • 通信作者: 张贺, 陈家隆
  • 基金资助:
    国家自然科学基金(82103879); 广东省基础与应用基础研究基金联合基金粤莞培育项目(2021B1515140032); 广东省中医药局科研项目面上项目(20222104); 广东省“冲补强”广东医科大学学科建设项目(4SG22021G)

Rotenone promotes ferroptosis of dopaminergic neurons by reducing the expression of MCU protein

Ailun Xie, Dongyan Zheng, Ziwei Cai, Renjian Lu, Yongming Peng, He Zhang(), Jialong Chen()   

  1. Department of Preventive Medicine, School of Public Health, Guangdong Medical University, Dongguan Guangdong 523808, China
  • Received:2022-11-06 Published:2023-05-28
  • Corresponding author: He Zhang, Jialong Chen
引用本文:

谢艾伦, 郑冬燕, 蔡紫薇, 卢仁建, 彭永明, 张贺, 陈家隆. 鱼藤酮通过降低线粒体钙离子单向转运体蛋白表达促进多巴胺能神经元铁死亡[J/OL]. 中华临床实验室管理电子杂志, 2023, 11(02): 71-78.

Ailun Xie, Dongyan Zheng, Ziwei Cai, Renjian Lu, Yongming Peng, He Zhang, Jialong Chen. Rotenone promotes ferroptosis of dopaminergic neurons by reducing the expression of MCU protein[J/OL]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2023, 11(02): 71-78.

目的

研究线粒体钙离子单向转运体(MCU)参与调控鱼藤酮诱导多巴胺能神经元铁死亡的作用机制。

方法

运用免疫印迹试验和脂质氧化等试剂盒检测鱼藤酮处理细胞前后MCU蛋白表达水平及铁死亡水平,检测鱼藤酮干预同时上调MCU蛋白表达,铁死亡水平的变化。

结果

鱼藤酮处理后多巴胺能神经元谷胱甘肽(GSH)过氧化物酶-4、铁蛋白重链多肽1蛋白表达下降,胞内氧化应激水平上升;MCU蛋白表达下降,而恢复MCU蛋白表达水平后,铁死亡水平下降。

结论

鱼藤酮通过降低MCU蛋白表达促进多巴胺能神经元铁死亡。

Objective

To study the mechanism of mitochondrial calcium uniporter (MCU) in regulating rotenone induced ferroptosis in dopaminergic neurons.

Methods

Immunoblotting test and lipid oxidation kit were used to detect the expression of MCU protein and the level of ferroptosis before and after rotenone treatment. The changes of the expression of MCU protein and the level of ferroptosis after rotenone treatment were detected.

Results

After rotenone treatment, the expression of glutathione peroxidase - 4 and ferritin heavy chain polypeptide - 1 protein in dopaminergic neurons were decreased, and the level of intracellular oxidative stress was increased; the expression of MCU protein and the level of ferroptosis were decreased after the recovery of MCU protein expression.

Conclusions

Rotenone can promote ferroptosis of dopaminergic neurons by reducing the expression of MCU protein.

表1 小鼠黑质神经元SN4741细胞需要配制专用培养基
图1 鱼藤酮对小鼠多巴胺能神经元的影响注:1A. 鱼藤酮处理SN4741细胞24 h后TH、a-synclein蛋白表达变化(免疫印迹);1B. 与CTR组比较,aP<0.05。
图2 鱼藤酮对多巴胺能神经元铁死亡的影响注:2A-2B. 电镜下观察鱼藤酮处理前后SN4741线粒体形态的变化(标尺500 nm);2C-2D. 鱼藤酮处理SN4741细胞24 h后铁死亡相关蛋白表达变化;2E. 鱼藤酮处理SN4741细胞24 h后细胞MDA水平变化;2F. 鱼藤酮处理SN4741细胞24 h后细胞GSH水平变化。与CTR比较,aP<0.05。
图3 鱼藤酮对MCU蛋白表达的影响注:鱼藤酮处理SN4741细胞24 h后MCU蛋白表达变化。与CTR比较,aP<0.05。
图4 MCU对鱼藤酮诱导多巴胺能神经元铁死亡的影响注:4A-4D. 精胺(Sper)和过表达MCU处理SN4741细胞后MCU和铁死亡相关蛋白表达变化;4E-4F. 精胺(Sper)处理SN4741细胞24 h后细胞GSH和MDA水平变化;4G-4H. 过表达MCU处理SN4741细胞后细胞GSH和MDA水平变化。与Rot组比较,aP<0.05;与CTR组比较,bP<0.05。
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