School of Life sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Redox Rep. 2021 Dec;26(1):53-61. doi: 10.1080/13510002.2021.1901028.
: 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.: We analyzed patterns of cytosolic and mitochondrial HO 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.: We found that the level of mitochondrial HO greatly increased compared to cytosolic HO and it affected cytosolic HO generation after glutamate treatment. In addition, we confirmed that mitochondrial Prx5 provides more effective neuroprotection than cytosolic Prx5.: 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.
虽然谷氨酸是神经元系统的必需因素，但过量的谷氨酸会产生兴奋性毒性。我们之前报道过，过氧化物酶 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，尚不清楚细胞质或线粒体 Prx5 提供更大的神经保护作用。在这里，我们研究了细胞质和线粒体 Prx5 的神经保护作用的差异。
我们使用 HyPer 蛋白分析了谷氨酸毒性中细胞质和线粒体 HO 生成的模式。然后，我们用相应的方法证实了细胞内 ROS 水平和细胞凋亡的变化。通过共聚焦显微镜成像和 Western blot 评估线粒体动力学。
我们发现，与细胞质 HO 相比，线粒体 HO 的水平大大增加，并且它影响谷氨酸处理后的细胞质 HO 的生成。此外，我们证实线粒体 Prx5 比细胞质 Prx5 提供更有效的神经保护作用。
总的来说，我们的研究揭示了谷氨酸毒性中细胞质和线粒体 ROS 的机制。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，控制这些因素对于预防神经退行性疾病可能是有用的。
