Knockdown of peroxiredoxin V increases glutamate‑induced apoptosis in HT22 hippocampal neuron cells

Shen, Gui‐Nan; Liu, Lei; Li, Feng; Yu, Jin; Jin, Meihua; Han, Ying‐Hao; Jin, Cheng‐Hao; Jin, Yong-Zhe; Lee, Dong-Soek; Kwon, Tai Hun; Cui, Yudong; Sun, Haiyan

doi:10.3892/mmr.2018.8826

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…The activation of ERKs has been revealed to contribute to neuronal cell death in certain in vitro models of neurotoxicity. Persistent activation of ERK1/2 contributes to glutamate-induced oxidative toxicity (42–45), which is consistent with the results of the present study. ERK also contributes to cell death through the suppression of anti-apoptotic signaling molecule RAC-α serine/threonine-protein kinase (34).…”

Section: Discussionsupporting

confidence: 93%

Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally‑induced diabetes mellitus

Zhu

Wang

et al. 2019

Mol Med Report

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Glutamate-induced excitotoxicity in the striatum has an important role in neurodegenerative diseases. It has been reported that diabetes mellitus (DM) induces excitotoxicity in striatal neurons, although the underlying mechanism remains to be fully elucidated. The present study aimed to investigate the effect of gastrodin on DM-induced excitotoxicity in the striatal neurons of diabetic rats. Adult Sprague-Dawley rats were divided into control, diabetic, and gastrodin intervention groups. Diabetes in the rats was induced with a single intraperitoneal injection of streptozotocin (65 mg/kg). In the gastrodin groups, the rats were gavaged with 60 or 120 mg/kg/day gastrodin for 6 weeks, 3 weeks following the induction of diabetes. Pathological alterations in the striatum were assessed using hematoxylin and eosin (H&E) staining. The protein expression levels of phosphorylated (p)-extracellular signal-regulated kinase (ERK)1/2, p-mitogen-activated protein kinase kinase (MEK)1/2, tyrosine receptor kinase B (TrKB) and brain-derived neurotrophic factor (BDNF) in the striatal neurons were evaluated by western blotting and double immunofluorescence. Additionally, the extracellular levels of glutamate were measured by microanalysis followed by high-pressure-liquid-chromatography. In diabetic rats, striatal neuronal degeneration was evident following H&E staining, which revealed the common occurrence of pyknotic nuclei. This was coupled with an increase in glutamate levels in the striatal tissues. The protein expression levels of p-ERK1/2, p-MEK1/2, TrKB and BDNF in the striatal tissues were significantly increased in the diabetic rats compared with those in the normal rats. In the gastrodin groups, degeneration of the striatal neurons was ameliorated. Furthermore, the expression levels of glutamate, p-ERK1/2, p-MEK1/2, TrKB and BDNF in the striatal neurons were decreased. From these findings, it was concluded that reduced neurotoxicity in striatal neurons following treatment with gastrodin may be attributed to its suppressive effects on the expression of p-ERK1/2, p-MEK1/2, BDNF and TrKB.

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Section: Discussionsupporting

confidence: 93%

Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally‑induced diabetes mellitus

Zhu

Wang

et al. 2019

Mol Med Report

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“…The present study showed that co-treatment with N-acetyl-L-cysteine (an intensive ROS scavenger) or MitoTEMPO (a mitochondrial ROS scavenger) downregulated Prx5 expression, indicating that the upregulation of Prx5 was related to glutamate-induced ROS generation (Figure 1(C)). These results are corresponded to previous study [18]. Since Prx5 is known to be broadly dispersed inside cells, including in the cytosol and mitochondria [19], we confirmed the subcellular distribution of Prx5 induced by glutamate using cytosolic and mitochondrial cell fractions.…”

Section: Glutamate Upregulated the Expression Level Of Cytprx5 And Mtsupporting

confidence: 92%

“…Of the six Prx subtypes, the antioxidant effect of Prx5 in various cellular systems has been well established. In previous studies, we reported that Prx5 reduces LPS-induced microglia activation and protects neuronal cells from neurotoxic substances, such as β-amyloid, iron, diethylhexyl phthalate, and glutamate [13,18,[30][31][32][33][34]. These findings highlight the necessity of further study on the relationship between the antioxidant effects and intracellular location of Prx5.…”

Section: Discussionmentioning

confidence: 80%

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

Kim

Lee

et al. 2021

Redox Report

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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.

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“…Prx V is an atypical 2-cys-Prx which is widely expressed in cellular compartments. It has been reported that Prx V is involved in cellular apoptosis induced by oxidative stress in various cells such as Hela cervical cancer cells and HT22 hippocampus cells through several pathways (29)(30)(31). The role of Prx V in the apoptosis of GC cells has not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Jin

Sun

Liu

et al. 2019

In Vivo

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Background/Aim: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. Materials and Methods: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. Results: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of proapoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. Conclusion: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers. Gastric cancer (GC) is one of the most common malignancies worldwide; unfortunately, the majority of GC patients is diagnosed at an advanced stage and die within 24 months after surgery because of recurrence and metastasis (1). The cure rate of gastric cancer is extremely low and the risk of treatment is large. It is well known that reactive oxygen species ROS levels are high in cancer cells compared to normal cells. ROS such as hydrogen peroxide, superoxide anions etc. are produced during mitochondria metabolism (2). Low levels of ROS can act as second messengers by participating in a variety of cellular physiological activities such as signal transduction, apoptosis, aging, proliferation and migration of cells. On the contrary, high levels of ROS have been recognized as driving factors in numerous diseases including cancer, aging, neurodegenerative disease, diabetes, cardiovascular disease, stroke, and asthma (3, 4), by inducing lipid, protein and DNA oxidation (5) thereby resulting in increased cellular apoptosis. On the other hand, there are cellular antioxidant mechanisms that clear excessive ROS (6, 7), such as superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (Gpx) and peroxiredoxin (Prxs). Prx V is a member of the Prxs family, which plays crucial roles in protecting cells from oxidative stress. Prxs are 1183 This article is freely accessible online.

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Knockdown of peroxiredoxin V increases glutamate‑induced apoptosis in HT22 hippocampal neuron cells

Cited by 7 publications

References 38 publications

Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally‑induced diabetes mellitus

Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally‑induced diabetes mellitus

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

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

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