Comparison of the protective effect of cytosolic and mitochondrial Peroxiredoxin 5 against glutamate-induced neuronal cell death

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 H 2 O 2 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 H 2 O 2 greatly increased compared to cytosolic H 2 O 2 and it affected cytosolic H 2 O 2 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.

Moschus ameliorates glutamate-induced cellular damage by regulating autophagy and apoptosis pathway

“…It was found that Glu-induced cytotoxicity was associated with oxidative stress, mitochondrial imbalances, and autophagy imbalances 132 . Additionally, the apoptotic cell death caused by Glu toxicity was accelerated by mitochondrial dysfunction and ROS overproduction 133 . Therefore, Glu were selected as a damaging agent in this study.…”