Edaravone Protects <scp>HT</scp>22 Neurons from H2O2‐induced Apoptosis by Inhibiting the <scp>MAPK</scp> Signaling Pathway

Zhao, Zhongyan; Luan, Ping; Huang, Shixiong; Xiao, Shifu; Zhao, Jia; Zhang, Bei; B, Gu; Pi, Rongbiao; Li, Jun

doi:10.1111/cns.12044

Cited by 93 publications

(78 citation statements)

References 35 publications

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“…UA has been demonstrated to trigger the upregulation of ROS in several cell types. ROS are able to regulate or induce multiple cellular processes, including epithelial-mesenchymal transition (19), growth (20), cell differentiation (21) and apoptosis (7)(8)(9)13). The present study indicated that UA induced apoptosis in renal tubular cells by inducing ROS, which may cause cell loss and tubular dysfunction during the progression of CKD.…”

Section: Discussionmentioning

confidence: 99%

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Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Sheng

Liu

et al. 2016

Molecular Medicine Reports

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Abstract. The purpose of the present study was to evaluate the effects of uric acid in promoting tubular cell apoptosis and verify the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4)-induced oxidative stress in this process. HK-2 cells were used as a human proximal tubular cell model and co-cultured with various concentrations of uric acid with or without pre-treatment with the Nox4 inhibitor diphenylene iodonium (DPI). The apoptotic rate and the amount of reactive oxygen species (ROS) were examined by flow cytometry. Furthermore, levels of Nox4, phosphorylated (p)-P38, p-extracellular signal-regulated kinase (ERK), B-cell lymphoma 2 (Bcl-2) and Bcl-2-extra large (Bax) were detected by western blot analysis. The results showed that treatment with uric acid decreased HK-2 cell viability and promoted apoptosis in a dose-dependent manner. This was paralleled with an upregulation of Nox4 as well as ROS overproduction, which activated the phosphorylation of P38/ERK and caused an imbalance of Bax/Bcl-2 in HK-2 cells. Of note, inhibition of Nox4 with DPI prevented uric acid-induced cell injury by suppressing ROS generation and P38/ERK activation. In conclusion, it was demonstrated that elevated uric acid promoted ROS-induced tubular cell apoptosis by upregulating Nox4 expression. The present study therefore provided possible mechanisms and a potential therapeutic target of uric acid-induced chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that mitogen-activated protein kinase (MAPK) pathways are activated by upregulation of intracellular ROS (12)(13)(14). P38 and ERK1/2 are important members of the MAPK family, which regulates cell growth and apoptosis (15)(16)(17).…”

Section: P38 and Erk1/2 Signaling Are Involved In Ua-induced Apoptosismentioning

confidence: 99%

Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Sheng

Liu

et al. 2016

Molecular Medicine Reports

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“…17,18) To measure the cytosolic Ca 2+ concentration, the cells were incubated with 20 µM Fluo-4/AM and 1 µM pluronic F-127 for 20 min at 37°C in the dark. Fluorescence images were obtained using confocal laser-scanning microscopy, with 488 nm excitation wavelength and 510 nm detection wavelength.…”

Section: +mentioning

confidence: 99%

Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel

Hao

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial K ATP (mitoK ATP ) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca 2 overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoK ATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury. Key words vitamin C (VC); ischemia/reperfusion (I/R) injury; ischemic post-treatment; mitochondrial K ATP (mitoK ATP ) channelIn recent years, cardiovascular disease has become a great threat to human life and health. Prolonged myocardial ischemia can cause tissue damage and even cell death. A key treatment of coronary heart disease is blood reperfusion of the myocardium. However, restoration of blood supply followed by myocardial cell function and structural damage results in a pathophysiological state known as ischemia/reperfusion (I/R) injury.1) The reduction occurrence of I/R injury has become a focus of current research.In 1986, Murry first put forward a self-defensive protective mechanism of the myocardial cell known as myocardial ischemia preadaptation (ischemic preconditioning; IPC), and transient ischemic preconditioning can improve myocardial ischemia and reperfusion of longer than damage tolerance ability.2) However, ischemic preconditioning poses challenges including safety and operability, and individual differences of clinical application of IPC is restricted. Thus, several studies have proposed drug post-treatment (pharmacological preconditioning; PPC), namely the simulation of IPC via a variety of drugs result in less I/R injury. 3)In myocardial I/R injury, the integrity of the mitochondrial membrane and its functions have undergone major changes, such as depolarization of the mitochondrial membrane potential (ΔΨm), interruption of mitochondrial respiratory chain electron transfer, inhibi...

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“…H 2 O 2 generation is required to mediate the complete sequence of events occurring in oxidative stress-induced neuronal cell death. 24) In previous studies, researchers employed H 2 O 2 overload as a neurotoxic challenge paradigm to evaluate aspects of neuroprotection in murine hippocampal HT22 cell. 25,26) The neuroprotective effect of C. (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Corydalis ternata Extract and Its Phytochemical Quantitative Analysis

et al. 2017

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The tubers of Corydalis ternata have been used to treat cardiovascular diseases such as hypertension and cardiac arrhythmia. Its active components have anticholinesterase, antiamnesic, and anti-inflammatory activities, and analgesic effects. In the present study, we performed quantitative analyses of the two components of C. ternata, coptisine and berberine, using HPLC. A 70% ethanol extract of C. ternata was prepared and the two components were separated using a C-18 analytical column on a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. Recordings were performed at a UV wavelength of 265 nm for two standard components. The established analytical method showed high linearity (correlation coefficient (r) 1.0000) and proper precision (0.49-3.88%), accuracy (97.88-102.7%), and recovery (95.12-103.79%) for two standard components. The amount of the coptisine and berberine was 4.968 0.089 mg/g and 3.73 0.075 mg/g, respectively. In addition, we investigated the effects of coptisine and berberine on acetylcholinesterase activity and amyloid-β aggregation, which are major biomarkers of dementia. Coptisine and berberine decreased acetylcholinesterase activity in a dose-dependent manner (IC 50 0.74 and 0.48 µM, respectively). The C. ternata extract exerted an antioxidant activity by stimulating the radical scavenging activity of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), but not 2,2-diphenyl-1-picrylhydrazyl (DPPH). Furthermore, the C. ternata extract reversed the hydrogen peroxide-induced death of HT22 hippocampal cells, indicating its neuroprotective effect. Our results suggest the potential of C. ternata as a therapeutic agent against dementia via the inhibition of acetylcholinesterase activity and neuronal cell death.

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Edaravone Protects HT22 Neurons from H₂O₂‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway

Cited by 93 publications

References 35 publications

Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial K<sub>ATP</sub> Channel

Neuroprotective Effect of <i>Corydalis ternata</i> Extract and Its Phytochemical Quantitative Analysis

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Edaravone Protects HT22 Neurons from H2O2‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway

Cited by 93 publications

References 35 publications

Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Nox4 has a crucial role in uric acid-induced oxidative stress and apoptosis in renal tubular cells

Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial K<sub>ATP</sub> Channel

Neuroprotective Effect of <i>Corydalis ternata</i> Extract and Its Phytochemical Quantitative Analysis

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Edaravone Protects HT22 Neurons from H₂O₂‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway