Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus.

Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus.

Publication date: Mar 23, 2020

Iron is an essential element for cellular functions, including those of neuronal cells. However, an imbalance of iron homeostasis, such as iron overload, has been observed in several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Iron overload causes neuronal toxicity through mitochondrial fission, dysregulation of Ca, ER-stress, and ROS production. Nevertheless, the precise mechanisms between iron-induced oxidative stress and iron toxicity related to mitochondria and endoplasmic reticulum (ER) in vivo are not fully understood. Here, we demonstrate the role of peroxiredoxin 5 (Prx5) in iron overload-induced neurotoxicity using Prx5-deficient mice. Iron concentrations and ROS levels in mice fed a high iron diet were significantly higher in Prx5 mice than wildtype (WT) mice. Prx5 deficiency also exacerbated ER-stress and ER-mediated mitochondrial fission via Ca/calcineurin-mediated dephosphorylation of Drp1 at Serine 637. Moreover, immunoreactive levels of cleaved caspase3 in the CA3 region of the hippocampus were higher in iron-loaded Prx5 mice than WT mice. Furthermore, treatment with N-acetyl-cysteine, a reactive oxygen species (ROS) scavenger, attenuated iron overload-induced hippocampal damage by inhibiting ROS production, ER-stress, and mitochondrial fission in iron-loaded Prx5 mice. Therefore, we suggest that iron overload-induced oxidative stress and ER-mediated mitochondrial fission may be essential for understanding iron-mediated neuronal cell death in the hippocampus and that Prx5 may be useful as a novel therapeutic target in the treatment of iron overload-mediated diseases and neurodegenerative diseases.

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Lee, D.G., Kam, M.K., , Lee, Lee, H.J., and Lee, D.S. Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus. 24454. 2020 Cell Death Dis (11):3.

Concepts Keywords
Acetyl Parkin
Alzheimer Neurodegeneration
CA3 Oxidative stress
Calcineurin Mitochondrion
Cysteine DNM1L
Dephosphorylation Mitochondrial fission
Endoplasmic Reticulum Reactive oxygen species
ER Human iron metabolism
ER Stress Senescence
Hippocampal Branches of biology
Hippocampus Peroxiredoxin deficiency
Homeostasis Neurodegenerative diseases
Iron Disease Iron overload
Iron Overload
Mice
Mitochondria
Mitochondrial Fission
Neurodegenerative Diseases
Neurotoxicity
Oxidative Stress
Oxygen
Parkinson
Peroxiredoxin
ROS
Scavenger
Serine
Toxicity
Vivo
Wildtype

Semantics

Type Source Name
disease MESH iron overload
disease MESH death
drug DRUGBANK Iron
disease MESH neurodegenerative diseases
disease MESH oxidative stress
drug DRUGBANK Serine
drug DRUGBANK L-Cysteine

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