Peroxiredoxin 5 prevents iron overload-induced neuronal death by inhibiting mitochondrial fragmentation and endoplasmic reticulum stress in mouse hippocampal HT-22 cells

Lee, Dong Seok; Kam, Min Kyoung; Kim, Kyung Min; Kim, Han Seop; Kwon, Oh Nam; Lee, Hyun‐Shik

doi:10.1016/j.biocel.2018.06.005

Cited by 30 publications

(27 citation statements)

References 53 publications

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“…RNA interference assay. Once the HT22 cells reached 50% confluence, they were transfected with 10pmol of short interfering RNA (siRNA) against Prx5 (siPrx5; Bioneer, Daejeon, South Korea) using Lipofectamine RNAiMAX (Thermo Fisher Scientific, MA) as previously described (16,62). The siRNA sequences were the following: siPrx5 sense, 5=-GUCUGAGCGUUAAUGACGU-3=; siPrx5 antisense, 5=-ACG UCAUUAACGCUCAGAC-3=.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, since Prx5 is located within the cytosol and the mitochondria, it can effectively remove intracellular ROS (15). Previous studies have determined that Prx5 is a potent antioxidant enzyme that contributes to cellular homeostasis by scavenging intracellular ROS (16)(17)(18)(19). However, the role of Prx5 in protection against glutamate-induced neuronal cell death remains unclear.…”

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confidence: 99%

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Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

Kim

Lee

et al. 2019

Molecular and Cellular Biology

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Glutamate is an essential neurotransmitter in the central nervous system (CNS). However, high glutamate concentrations can lead to neurodegenerative diseases. A hallmark of glutamate toxicity is high levels of reactive oxygen species (ROS), which can trigger Ca2+ influx and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Peroxiredoxin 5 (Prx5) is a well-known cysteine-dependent peroxidase enzyme. However, the precise effects of Prx5 on glutamate toxicity are still unclear. In this study, we investigated the role of Prx5 in glutamate-induced neuronal cell death. We found that glutamate treatment induces endogenous Prx5 expression and Ca2+/calcineurin-dependent dephosphorylation of Drp1, resulting in mitochondrial fission and neuronal cell death. Our results indicate that Prx5 inhibits glutamate-induced mitochondrial fission through the regulation of Ca2+/calcineurin-dependent dephosphorylation of Drp1, and it does so by scavenging cytosolic and mitochondrial ROS. Therefore, we suggest that Ca2+/calcineurin-dependent mitochondrial dynamics are deeply associated with glutamate-induced neurotoxicity. Consequently, Prx5 may be used as a potential agent for developing therapies against glutamate-induced neurotoxicity and neurodegenerative diseases where it plays a key role.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

Kim

Lee

et al. 2019

Molecular and Cellular Biology

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“…Peroxiredoxin 5 is an anti-oxidant enzyme that decreases hydrogen peroxide and alkyl hydroperoxide. It plays a critical role in cellular homeostasis by scavenging cellular ROS and ameliorates glutamate-induced apoptosis in neuronal cells culture [14,15]. Moreover, knockdown of peroxiredoxin 5 increases apoptosis caused by glutamate exposure [16].…”

Section: Discussionmentioning

confidence: 99%

Identification of proteins differentially expressed by glutamate treatment in cerebral cortex of neonatal rats

2019

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Glutamate leads to neuronal cell damage by generating neurotoxicity during brain development. The objective of this study is to identify proteins that differently expressed by glutamate treatment in neonatal cerebral cortex. Sprague-Dawley rat pups (post-natal day 7) were intraperitoneally injected with vehicle or glutamate (10 mg/kg). Brain tissues were isolated 4 h after drug treatment and fixed for morphological study. Moreover, cerebral cortices were collected for protein study. Two-dimensional gel electrophoresis and mass spectrometry were carried out to identify specific proteins. We observed severe histopathological changes in glutamate-exposed cerebral cortex. We identified various proteins that differentially expressed by glutamate exposure. Identified proteins were thioredoxin, peroxiredoxin 5, ubiquitin carboxy-terminal hydrolase L1, proteasome subunit alpha proteins, isocitrate dehydrogenase, and heat shock protein 60. Heat shock protein 60 was increased in glutamate exposed condition. However, other proteins were decreased in glutamate-treated animals. These proteins are related to anti-oxidant, protein degradation, metabolism, signal transduction, and anti-apoptotic function. Thus, our findings can suggest that glutamate leads to neonatal cerebral cortex damage by regulation of specific proteins that mediated with various functions.

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“…The cells were then harvested by trypsinization. The intracellular ROS was then determined using flow cytometry following the methods described before [28].…”

Section: Ros Production Determined By Flow Cytometrymentioning

confidence: 99%

ERRα activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption

Zhang

et al. 2020

Bioscience Reports

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Lapatinib, a tyrosine kinase inhibitor, can initially benefit the patients with breast tumors but fails in later treatment due to the inevitable development of drug resistance. Estrogen-related receptor α (ERRα) modulates the metabolic adaptations in lapatinib-resistant cancer cells; however, the underlying mechanism remains unclear. ERRα was predicted to bind to the serine hydroxymethyltransferase 2 (SHMT2) transcription initiation site in the ER- and HER2-positive cell line BT-474; thus, we hypothesize that ERRα might modulate the resistance of breast cancer to lapatinib via regulating SHMT2. In the present study, we revealed that 2.5 and 5 µM lapatinib treatment could significantly decrease the expression and protein levels of ERRα and SHMT2; ERRα and SHMT2 expression and protein levels were significantly up-regulated in breast cancer cells, in particularly in breast cancer cells with resistance to lapatinib. ERRα knockdown restored the inhibitory effects of lapatinib on the BT-474R cell viability and migration; in the meantime, ERRα knockdown rescued the production of reactive oxygen species (ROS) whereas decreased the ratio of glutathione (GSH)/oxidized glutathione (GSSG) upon lapatinib treatment. Via targeting SHMT2 promoter region, ERRα activated the transcription of SHMT2. The effects of ERRα knockdown on BT-474R cells under lapatinib treatment could be significantly reversed by SHMT2 overexpression. In conclusion, ERRα knockdown suppresses the detoxification and the mitochondrial metabolic adaption in breast cancer resistant to lapatinib; ERRα activates SHMT2 transcription via targeting its promoter region, therefore enhancing breast cancer resistance to lapatinib.

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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

Cited by 30 publications

References 53 publications

Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

Identification of proteins differentially expressed by glutamate treatment in cerebral cortex of neonatal rats

ERRα activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption

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