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Comparison of the protective effect of cytosolic and mitochondrial Peroxiredoxin 5 against glutamate-induced neuronal cell death
Redox Report ( IF 5.2 ) Pub Date : 2021-03-15 , DOI: 10.1080/13510002.2021.1901028
Mi Hye Kim 1, 2 , Da Yeon Kim 3 , Hong Jun Lee 4, 5 , Young-Ho Park 6 , Jae-Won Huh 7 , Dong-Seok Lee 1, 2
Affiliation  

ABSTRACT

Objectives: Although glutamate is an essential factor in the neuronal system, excess glutamate can produce excitotoxicity. We previously reported that Peroxiredoxin 5 (Prx5) protects neuronal cells from glutamate toxicity via its antioxidant effects. However, it is unclear whether cytosolic or mitochondrial Prx5 provides greater neuroprotection. Here, we investigated differences in the neuroprotective effects of cytosolic and mitochondrial Prx5.

Methods: We analyzed patterns of cytosolic and mitochondrial H2O2 generation in glutamate toxicity using HyPer protein. And then, we confirmed the change of intracellular ROS level and apoptosis with respective methods. The mitochondrial dynamics was assessed with confocal microscope imaging and western blotting.

Results: We found that the level of mitochondrial H2O2 greatly increased compared to cytosolic H2O2 and it affected cytosolic H2O2 generation after glutamate treatment. In addition, we confirmed that mitochondrial Prx5 provides more effective neuroprotection than cytosolic Prx5.

Discussion: Overall, our study reveals the mechanisms of cytosolic and mitochondrial ROS in glutamate toxicity. Our findings suggest that mitochondrial ROS and Prx5 are attractive therapeutic targets and that controlling these factors be useful for the prevention of neurodegenerative diseases.



中文翻译:

细胞溶质和线粒体 Peroxiredoxin 5 对谷氨酸诱导的神经元细胞死亡的保护作用的比较

摘要

目的:虽然谷氨酸是神经元系统中的一个重要因素,但过量的谷氨酸会产生兴奋性毒性。我们之前报道过 Peroxiredoxin 5 (Prx5) 通过其抗氧化作用保护神经元细胞免受谷氨酸毒性。然而,尚不清楚细胞溶质或线粒体 Prx5 是否提供更大的神经保护作用。在这里,我们研究了细胞溶质和线粒体 Prx5 的神经保护作用的差异。

方法:我们使用 HyPer 蛋白分析了谷氨酸毒性中细胞溶质和线粒体 H 2 O 2生成的模式。然后,我们用各自的方法证实了细胞内ROS水平和细胞凋亡的变化。用共聚焦显微镜成像和蛋白质印迹评估线粒体动力学。

结果:我们发现线粒体H 2 O 2的水平与细胞溶质H 2 O 2相比大大增加,并且它影响谷氨酸处理后细胞溶质H 2 O 2的生成。此外,我们证实线粒体 Prx5 提供比细胞溶质 Prx5 更有效的神经保护作用。

讨论:总的来说,我们的研究揭示了细胞溶质和线粒体活性氧在谷氨酸毒性中的作用机制。我们的研究结果表明,线粒体 ROS 和 Prx5 是有吸引力的治疗靶点,控制这些因素有助于预防神经退行性疾病。

更新日期:2021-03-15
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