scholarly journals Neuroprotective Effect of Gallocatechin Gallate on Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1387
Author(s):  
Do Hwi Park ◽  
Jun Yeon Park ◽  
Ki Sung Kang ◽  
Gwi Seo Hwang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Nuclear Condensation ◽  
Epicatechin Gallate ◽  
Ht22 Cells ◽  
Gallocatechin Gallate

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.

scholarly journals Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells

2019 ◽  
Vol 43 (2) ◽  
pp. 326-334 ◽  
Author(s):  
Dong Hoi Kim ◽  
Dae Won Kim ◽  
Bo Hyun Jung ◽  
Jong Hun Lee ◽  
Heesu Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Ginsenoside Rb2

scholarly journals Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 144 ◽  
Author(s):  
Chang-Hyun Park ◽  
Ji Hoon Song ◽  
Su-Nam Kim ◽  
Ji Hwan Lee ◽  
Hae-Jeung Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protein Kinases ◽  
Apoptotic Cell ◽  
Curcuma Longa ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

scholarly journals P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus

2020 ◽  
Vol 21 (24) ◽  
pp. 9496
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Ht22 Cells ◽  
H2o2 Treatment ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 μM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 μM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

scholarly journals Neuroprotective γ-Pyrones from Fusarium Solani JS-0169: Cell-Based Identification of Active Compounds and an Informatics Approach to Predict the Mechanism of Action

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 91 ◽  
Author(s):  
Hyun Gyu Choi ◽  
Ji Hoon Song ◽  
Musun Park ◽  
Soonok Kim ◽  
Chang-Eop Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Fusarium Solani ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuroprotective Activity ◽  
Glutamate Toxicity ◽  
Protective Effects ◽  
Cns Injury ◽  
Ht22 Cells

Glutamate toxicity has been implicated in neuronal cell death in both acute CNS injury and in chronic diseases. In our search for neuroprotective agents obtained from natural sources that inhibit glutamate toxicity, an endophytic fungus, Fusarium solani JS-0169 isolated from the leaves of Morus alba, was found to show potent inhibitory activity. Chemical investigation of the cultures of the fungus JS-0169 afforded isolation of six compounds, including one new γ-pyrone (1), a known γ-pyrone, fusarester D (2), and four known naphthoquinones: karuquinone B (3), javanicin (4), solaniol (5), and fusarubin (6). To identify the protective effects of the isolated compounds (1–6), we assessed their inhibitory effect against glutamate-induced cytotoxicity in HT22 cells. Among the isolates, compound 6 showed significant neuroprotective activity on glutamate-mediated HT22 cell death. In addition, the informatics approach using in silico systems pharmacology identified that compound 6 may exert its neuroprotective effect by controlling the amount of ubiquinone. The results suggest that the metabolites produced by the endophyte Fusarium solani JS-0169 might be related to the neuroprotective activity of its host plant, M. alba.

scholarly journals Comprehensive Insight of Neurodegenerative Diseases and The Role of Neurotoxin Agents — Glutamate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hui-Min Yap ◽  
Kwan-Liang Lye ◽  
Loh Teng-Hern Tan
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Monosodium Glutamate ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Glutamate Toxicity ◽  
Extracellular Glutamate

The increased concentration of extracellular glutamate has been reported to play a key role in most of the neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, even though its importance as an amino acid neurotransmitter in mammalian. Glutamate toxicity, which can be caused by excessive intake of monosodium glutamate (MSG), is the major contributor to pathological neuronal cell death. It causes neuronal dysfunction and degeneration in the central nervous system (CNS). Glutamate neurotoxicity can be categorized into two forms, which are receptor-mediated glutamate excitotoxicity and non-receptor mediated glutamate oxidative toxicity. The receptor-mediated glutamate excitotoxicity involved excessive stimulation of glutamate receptors (GluRs) which lead to excessive ion calcium (Ca2+) influx and activates a cell death cascade involving the accumulation of mitochondrially generated reactive oxygen species (ROS). Studies showed excessive extracellular glutamate leads to nerve cell death via the activation of N-methyl-Daspartate (NMDA) receptors in the cases of trauma or stroke. Whereas non-receptor mediated oxidative toxicity involved the breakdown of the cystine/glutamate antiporter (xc - ) mechanism, which leads to the depletion of glutathione (GSH) and causes oxidative stress and cell death. The cystine/glutamate antiporter couples the import of cystine to the export of glutamate. The increased concentration of extracellular glutamate could inhibit the uptake of cystine, which is required for the synthesis of the intracellular antioxidant GSH. GSH plays an important role in the disposal of peroxides by brain cells and in the protection against ROS. Depletion of GSH renders the cell to oxidative stress and ultimately leading to cell death. This article aims to provide a comprehensive review of neurodegenerative diseases and the role of neurotoxin agents, glutamate in these diseases.

scholarly journals STAT-Dependent Upregulation of 12/15-Lipoxygenase Contributes to Neuronal Injury after Stroke

2015 ◽  
Vol 35 (12) ◽  
pp. 2043-2051 ◽  
Author(s):  
Joo Eun Jung ◽  
Hulya Karatas ◽  
Yu Liu ◽  
Ayfer Yalcin ◽  
Joan Montaner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Injury Mechanism ◽  
Ht22 Cells ◽  
Signal Transducers ◽  
Human Stroke

Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and −1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke.

scholarly journals Cofilin1 oxidation links oxidative distress to mitochondrial demise and neuronal cell death

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Lena Hoffmann ◽  
Marcel S. Waclawczyk ◽  
Stephan Tang ◽  
Eva-Maria Hanschmann ◽  
Manuela Gellert ◽  
...  
Keyword(s):  
Cell Death ◽  
Cortical Neurons ◽  
Energy Demand ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mitochondrial Damage ◽  
Glutamate Excitotoxicity ◽  
Ht22 Cells ◽  
Cell Death Pathways ◽  
Regulated Necrosis

AbstractMany cell death pathways, including apoptosis, regulated necrosis, and ferroptosis, are relevant for neuronal cell death and share common mechanisms such as the formation of reactive oxygen species (ROS) and mitochondrial damage. Here, we present the role of the actin-regulating protein cofilin1 in regulating mitochondrial pathways in oxidative neuronal death. Cofilin1 deletion in neuronal HT22 cells exerted increased mitochondrial resilience, assessed by quantification of mitochondrial ROS production, mitochondrial membrane potential, and ATP levels. Further, cofilin1-deficient cells met their energy demand through enhanced glycolysis, whereas control cells were metabolically impaired when challenged by ferroptosis. Further, cofilin1 was confirmed as a key player in glutamate-mediated excitotoxicity and associated mitochondrial damage in primary cortical neurons. Using isolated mitochondria and recombinant cofilin1, we provide a further link to toxicity-related mitochondrial impairment mediated by oxidized cofilin1. Our data revealed that the detrimental impact of cofilin1 on mitochondria depends on the oxidation of cysteine residues at positions 139 and 147. Overall, our findings show that cofilin1 acts as a redox sensor in oxidative cell death pathways of ferroptosis, and also promotes glutamate excitotoxicity. Protective effects by cofilin1 inhibition are particularly attributed to preserved mitochondrial integrity and function. Thus, interfering with the oxidation and pathological activation of cofilin1 may offer an effective therapeutic strategy in neurodegenerative diseases.

Abstract P622: Regulation of Neuroprotective Myeloid Cell Leukemia 1 by Rapamycin and AT2R Agonists in Dopaminergic Neuronal Cell-line

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jamal Bajwa ◽  
Lakshmi Pulakat
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Line ◽  
Neuronal Damage ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Myeloid Cell ◽  
Serum Starvation ◽  
Cell Leukemia ◽  
Neuronal Cell Line

Myeloid Cell Leukemia I (MCL-1) is a critical protein for neuronal cell survival. MCL-1 is one of the anti-apoptotic proteins in the Bcl2 family. In neurons, MCL-1 regulates the rate of programmed cell death during development and after neuronal damage. It is now well established that without sufficient MCL-1 dopaminergic neuronal cells succumb to cell death under conditions of oxidative stress that result in neurodegenerative diseases such as Parkinsonism. Therefore, identifying drugs that can up-regulate the expression of MCL-1 in neuronal cells is critical for enhancing neuronal resistance to oxidative stress and improving neuronal survival. Aim of this study was to evaluate the effects of treatments with Rapamycin and a novel AT2R peptide agonist NP-6A4 on the MCL-1 expression in SH-SY5Y neuronal cell line. SH-SY5Y cells are a human-derived in vitro model of neuronal function and differentiation, expressing both adrenergic and dopaminergic markers. This cell line is a highly translational model for Parkinson's disease. Cells were maintained in a 1:1 mixture of DMEM and Ham's F-12 with 10% FBS. Cells were subjected to serum starvation and were treated with Rap (10nM), NP-6A4 (300nM) or their combination for 6 hours. MCL-1 protein expression was assessed by immunofluorescence using anti-MCL-1 antibody and a fluorophore-conjugated secondary antibody. Cells were imaged using a confocal microscope and fluorescence was quantified using Leica LAS AF software. It was observed that Rap treatment significantly suppressed MCL-1 expression in SH-SY5Y cells (~40% suppression, p<0.001), whereas Rap+NP-6A4 treatment reversed the Rap-mediated suppression of MCL-1 (p<0.0002). This data indicates that Rapamycin suppresses MCL-1 in dopaminergic neuronal cells and AT2R agonist, NP-6A4 is capable of reversing this effect.

scholarly journals Neuroprotective Activity of Methanolic Extract of Lysimachia christinae against Glutamate Toxicity in HT22 Cell and Its Protective Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gahee Ryu ◽  
Choong Je Ma
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Neuroprotective Activity ◽  
Glutamate Toxicity ◽  
Protective Mechanisms ◽  
Ht22 Cells ◽  
Ht22 Cell

Purpose. Excessive glutamate amount can give oxidative stress to neuronal cells, and the accumulation of cell death can trigger the neurodegenerative disorders. In this study, we discovered the neuroprotective effect of Lysimachia christinae Hance in the mouse hippocampal HT22 cell line. Method. Overnight incubated HT22 cells were pretreated with L. christinae extract dose dependently (1, 10, and 100 μg/ml). Followed by then, glutamate was treated. These treated cells were incubated several times again, and cell viability, accumulation of reactive oxygen species (ROS) and Ca2+, mitochondrial membrane potential (MMP), and glutathione-related enzyme amount were measured. Results. As a result, L. christinae increases the cell viability by inhibiting the ROS and Ca2+ formation, recovering the level of MMP and enhancing the activity of glutathione production compared with only vehicle-treated groups. Conclusion. These draw that L. christinae may remarkably decelerate the neurodegeneration by minimizing neuronal cell damage via oxidative stress.

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