scholarly journals Gossypitrin, A Naturally Occurring Flavonoid, Attenuates Iron-Induced Neuronal and Mitochondrial Damage

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3364
Author(s):  
María Ángeles Bécquer-Viart ◽  
Adonis Armentero-López ◽  
Daniel Alvarez-Almiñaque ◽  
Roberto Fernández-Acosta ◽  
Yasser Matos-Peralta ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Iron Homeostasis ◽  
Cell Damage ◽  
Protective Action ◽  
Neuronal Cell ◽  
Mitochondrial Damage ◽  
Atp Depletion ◽  
Neural Cells ◽  
Ht22 Cells ◽  
Naturally Occurring

The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC50 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos–Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.

scholarly journals A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

2011 ◽  
Vol 116 (1) ◽  
pp. 36-46 ◽  
Author(s):  
Yanier Núñez Figueredo ◽  
Laura García-Pupo ◽  
Osmany Cuesta Rubio ◽  
René Delgado Hernández ◽  
Zeki Naal ◽  
...  
Keyword(s):  
Cell Damage ◽  
Protective Action ◽  
Neuronal Cell ◽  
Naturally Occurring

FoxO3 transcription factor promotes autophagy after oxidative stress injury in HT22 cells

2020 ◽  
Author(s):  
Aiqing Deng ◽  
Limin Ma ◽  
Xueli Zhou ◽  
Xin Wang ◽  
Shouyan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Injury ◽  
Cell Damage ◽  
Critical Role ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Stress Injury ◽  
Oxidative Stress Injury

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-Methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H2O2-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.

Ferroptosis Is Regulated by Mitochondria in Neurodegenerative Diseases

2020 ◽  
Vol 20 (1) ◽  
pp. 20-34 ◽  
Author(s):  
Juepu Zhou ◽  
Yao Jin ◽  
Yuhong Lei ◽  
Tianyi Liu ◽  
Zheng Wan ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Iron Homeostasis ◽  
Cell Metabolism ◽  
Lipid Peroxide ◽  
Mitochondrial Damage ◽  
Mitochondrial Activity ◽  
Dependent Form

Background: Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases. Summary: In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.

scholarly journals MAPK Pathway Inhibitors Attenuated Hydrogen Peroxide Induced Damage in Neural Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhenwei Fan ◽  
Xuan Wang ◽  
Min Zhang ◽  
Chunshan Zhao ◽  
Chunli Mei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Mapk Pathway ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Neural Cell ◽  
Cell Stress ◽  
Mitogen Activated Protein Kinase ◽  
Neural Cells ◽  
Mapk Inhibitors

Background. Oxidative stress due to reactive oxygen species plays a central role in pathophysiology of neurodegenerative diseases. Inhibition of mitogen-activated protein kinase (MAPK) cascades attenuates the oxidative induced cell stress and behaves as potential neuroprotection agent. Materials and Methods. In this study, we evaluate hydrogen peroxide induced neural cell stress and determine how different MAPK inhibitors restore the cell damage. Results. The results indicated that oxidative stress induced by neural cell damage commonly exists, and MAPK inhibitors partially and selectively attenuated the cell damage by reducing ROS production and cell apoptosis. The cultured neurons are more susceptible to hydrogen peroxide than subculture cells. Conclusion. We conclude that the essential role of different MAPK inhibitors is to attenuate the hydrogen peroxide induced neuronal cell damage. Those data broaden the implication between individual neural cells and different MAPK inhibitors and give clues for oxidative stress induced neural diseases.

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.

scholarly journals Corticosterone Excess-Mediated Mitochondrial Damage Induces Hippocampal Neuronal Autophagy in Mice Following Cold Exposure

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 682
Author(s):  
Bin Xu ◽  
Limin Lang ◽  
Shize Li ◽  
Jianbin Yuan ◽  
Jianfa Wang ◽  
...  
Keyword(s):  
Cold Stress ◽  
Western Blotting ◽  
Cold Exposure ◽  
Mammalian Target Of Rapamycin ◽  
Neuronal Cell ◽  
Mitochondrial Damage ◽  
Ht22 Cells ◽  
Negative Effect

Cold stress can induce autophagy mediated by excess corticosterone (CORT) in the hippocampus, but the internal mechanism induced by cold stress is not clear. In vivo, male and female C57BL/6 mice were stimulated in 4 °C, 3 h per day for 1 week to build the model of cold sress. In vitro, hippocampal neuronal cell line (HT22) cells were incubated with or without mifepristone (RU486) for 1 h, then treated with 400 μM cortisol (CORT) for 3 h. In vivo, autophagy was measured by western blotting. In vitro, monodansylcadaverine staining, western blotting, flow cytometry, transmission electron microscopy, and immunofluorescence were used to characterize the mechanism of autophagy induced by excess CORT. Autophagy was shown in mouse hippocampus tissues following cold exposure, including mitochondrial damage, autophagy, and 5’ AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway activation after CORT treatment. Autophagy did not rely on the glucocorticoid receptor. In addition, autophagy in male mice was more severe. The study would provide new insight into the mechanisms and the negative effect of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.

scholarly journals FAM3A Protects HT22 Cells Against Hydrogen Peroxide-Induced Oxidative Stress Through Activation of PI3K/Akt but not MEK/ERK Pathway

2015 ◽  
Vol 37 (4) ◽  
pp. 1431-1441 ◽  
Author(s):  
Qing Song ◽  
Wen-Li Gou ◽  
Rong Zhang
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Cell Viability ◽  
Cell Damage ◽  
Ros Generation ◽  
Erk Pathway ◽  
Protective Effects ◽  
Ht22 Cells ◽  
Ldh Release

Background/Aims: Oxidative stress-induced cell damage is involved in many neurological diseases. FAM3A is the first member of family with sequence similarity 3 (FAM3) gene family and its biological function remains largely unknown. Methods: This study aimed to determine its role in hydrogen peroxide (H2O2) induced injury in neuronal HT22 cells. The protective effects were measured by cell viability, lactate dehydrogenase (LDH) release and apoptosis, and oxidative stress was assayed by reactive oxygen species (ROS) generation, ATP synthesis and lipid peroxidation. By using selective inhibitors, the involvement of PI3K/Akt and MEK/ERK pathways were also investigated. Results: The results of fluorescence staining revealed that H2O2 significantly decreased the expression of FAM3A protein, which was shown to be subcellularly located in mitochondria. Up-regulation of FAM3A by lentivirus transfection markedly increased cell viability and decreased LDH release after H2O2 treatment. The anti-apoptotic activity of FAM3A was demonstrated by the reduced mitochondrial cytochrome c release, decreased activation of caspase-3 and the results of flow cytometry. Overexpression of FAM3A attenuated intracellular ROS generation and loss of ATP production induced by H2O2, and subsequently inhibited lipid peroxidation. In addition, overexpression of FAM3A significantly increased the activation of Akt and ERK in H2O2 injured HT22 cells. By using Akt and ERK specific inhibitors, we found that inhibition of PI3K/Akt, but not MEK/ERK pathway, partially prevented FAM3A-induced protection against H2O2. Conclusion: These results suggest that FAM3A has protective effects against H2O2-induced oxidative stress by reducing ROS accumulation and apoptosis, and these protective effects are dependent on the activation of PI3K/Akt pathway.

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.

Mechanisms of Nickel-Induced Cell Damage in Allergic Contact Dermatitis and Nutritional Intervention Strategies

2020 ◽  
Vol 20 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
Dana Filatova ◽  
Christine Cherpak
Keyword(s):  
Lipid Peroxidation ◽  
Contact Dermatitis ◽  
Oxidative Damage ◽  
Allergic Contact Dermatitis ◽  
Cell Damage ◽  
Consumer Products ◽  
The Body ◽  
Cellular Damage ◽  
Nutritional Interventions ◽  
Allergic Contact

Background: Hypersensitivity to nickel is a very common cause of allergic contact dermatitis since this metal is largely present in industrial and consumer products as well as in some commonly consumed foods, air, soil, and water. In nickel-sensitized individuals, a cell-mediated delayed hypersensitivity response results in contact to dermatitis due to mucous membranes coming in long-term contact with nickel-containing objects. This process involves the generation of reactive oxidative species and lipid peroxidation-induced oxidative damage. Immunologically, the involvement of T helper (h)-1 and Th-2 cells, as well as the reduced function of T regulatory cells, are of importance. The toxicity, mutagenicity, and carcinogenicity of nickel are attributed to the generation of reactive oxygen species and induction of oxidative damage via lipid peroxidation, which results in DNA damage. Objective: The aim of this research is to identify nutritionally actionable interventions that can intercept nickel-induced cell damage due to their antioxidant capacities. Conclusion: Nutritional interventions may be used to modulate immune dysregulation, thereby intercepting nickel-induced cellular damage. Among these nutritional interventions are a low-nickel diet and an antioxidant-rich diet that is sufficient in iron needed to minimize nickel absorption. These dietary approaches not only reduce the likelihood of nickel toxicity by minimizing nickel exposure but also help prevent oxidative damage by supplying the body with antioxidants that neutralize free radicals.

scholarly journals Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3005
Author(s):  
Kanchan Bhardwaj ◽  
Ana Sanches Silva ◽  
Maria Atanassova ◽  
Rohit Sharma ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Experimental Data ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cell Damage ◽  
Cancer Growth ◽  
Naturally Occurring ◽  
Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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