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. 2018 Sep;102:10-19.
doi: 10.1016/j.biocel.2018.06.005. Epub 2018 Jun 12.

Peroxiredoxin 5 Prevents Iron Overload-Induced Neuronal Death by Inhibiting Mitochondrial Fragmentation and Endoplasmic Reticulum Stress in Mouse Hippocampal HT-22 Cells

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Peroxiredoxin 5 Prevents Iron Overload-Induced Neuronal Death by Inhibiting Mitochondrial Fragmentation and Endoplasmic Reticulum Stress in Mouse Hippocampal HT-22 Cells

Dong Gil Lee et al. Int J Biochem Cell Biol. .

Abstract

Iron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca2+, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood. In this study, we demonstrated that iron overload induces ROS production earlier in the ER than in the mitochondria, and peroxiredoxin 5 (Prx5), which is a kind of antioxidant induced by iron overload, prevents iron overload-induced mitochondrial fragmentation mediated by contact with ER and translocation of Drp1, by inhibiting ROS production and calcium/calcineurin pathway in HT-22 mouse hippocampal neuronal cells. Moreover, Prx5 also prevented iron overload-induced ER-stress and cleavage of caspase-3, which consequently attenuated neuronal cell death. Therefore, we suggested that iron overload induces oxidative stress in the ER earlier than in the mitochondria, thereby increasing ER stress and calcium levels, and consequently causing mitochondrial fragmentation and neuronal cell death. So we thought that this study is essential for understanding iron toxicity in neurons, and Prx5 may serve as a new therapeutic target to prevent iron overload-induced diseases and neurodegenerative disorders.

Keywords: Endoplasmic reticulum stress; Iron overload; Mitochondrial dynamics; Neurotoxicity; Oxidative stress; Peroxiredoxin 5.

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