scholarly journals Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Ji Jia ◽  
Lei Ma ◽  
Mingchun Wu ◽  
Lei Zhang ◽  
Xiajing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Metabolic Activity ◽  
Morphological Changes ◽  
Oxidative Injury ◽  
Ht22 Cells ◽  
Cb1 Antagonist ◽  
Ldh Release ◽  
Endogenous Cannabinoid

Background.Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA.Methods.The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression.Results.HT22 cells exposed to H2O2demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA.Conclusion.Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells.

scholarly journals Oxalate-induced activation of PKC-α and -δ regulates NADPH oxidase-mediated oxidative injury in renal tubular epithelial cells

2009 ◽  
Vol 297 (5) ◽  
pp. F1399-F1410 ◽  
Author(s):  
Vijayalakshmi Thamilselvan ◽  
Mani Menon ◽  
Sivagnanam Thamilselvan
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Cell Injury ◽  
Oxidative Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Ldh Release ◽  
Renal Tubular

Oxalate-induced oxidative stress contributes to cell injury and promotes renal deposition of calcium oxalate crystals. However, we do not know how oxalate stimulates reactive oxygen species (ROS) in renal tubular epithelial cells. We investigated the signaling mechanism of oxalate-induced ROS formation in these cells and found that oxalate significantly increased membrane-associated protein kinase C (PKC) activity while at the same time lowering cytosolic PKC activity. Oxalate markedly translocated PKC-α and -δ from the cytosol to the cell membrane. Pretreatment of LLC-PK1cells with specific inhibitors of PKC-α or -δ significantly blocked oxalate-induced generation of superoxide and hydrogen peroxide along with NADPH oxidase activity, LDH release, lipid hydroperoxide formation, and apoptosis. The PKC activator PMA mimicked oxalate's effect on oxidative stress in LLC-PK1cells as well as cytosol-to-membrane translocation of PKC-α and -δ. Silencing of PKC-α expression by PKC-α-specific small interfering RNA significantly attenuated oxalate-induced cell injury by decreasing hydrogen peroxide generation and LDH release. We believe this is the first demonstration that PKC-α- and -δ-dependent activation of NADPH oxidase is one of the mechanisms responsible for oxalate-induced oxidative injury in renal tubular epithelial cells. The study suggests that the therapeutic approach might be considered toward attenuating oxalate-induced PKC signaling-mediated oxidative injury in recurrent stone formers.

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 N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Jiying Jiang ◽  
Shuna Yu ◽  
Zhengchen Jiang ◽  
Cuihong Liang ◽  
Wenbo Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Mitochondrial Apoptosis ◽  
Sod Activity ◽  
Stress Injury ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

scholarly journals Pretreatment with Astragaloside IV protects human umbilical vein endothelial cells from hydrogen peroxide induced oxidative stress and cell dysfunction via inhibiting eNOS uncoupling and NADPH oxidase – ROS – NF-κB pathway

2016 ◽  
Vol 94 (11) ◽  
pp. 1132-1140 ◽  
Author(s):  
Chonghua Xu ◽  
Futian Tang ◽  
Meili Lu ◽  
Jing Yang ◽  
Ronghui Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Umbilical Vein ◽  
Astragaloside Iv ◽  
Enos Uncoupling ◽  
Umbilical Vein Endothelial Cells

Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular disorders. Astragaloside IV (AsIV) possesses potent antioxidant properties against oxidative stress through undefined mechanism(s). We sought to investigate whether AsIV protects human umbilical vein endothelial cells (HUVECs) from hydrogen peroxide (H2O2) induced oxidative stress focusing on eNOS uncoupling and the NADPH oxidase – ROS – NF-κB pathway. Compared with HUVECs incubated with H2O2 alone, pretreatment with AsIV significantly increased the viability of HUVECs, which was accompanied with apparent increase in nitric oxide (NO) production and decrease in intracellular superoxide anion production. Furthermore, pretreatment with AsIV increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH4) content, decreased Nox4 protein expression (the most abundant Nox isoform in HUVECs), inhibited translocation of NF-κB p65 subunit into nuclear fraction while enhanced the protein expression of IκB-α (the inhibitor of NF-κB p65), reduced the levels of IL-1β, IL-6, and TNF-α in HUVECs medium, and decreased iNOS protein expression. These results suggest that AsIV may protect HUVECs from H2O2-induced oxidative stress via inhibiting NADPH oxidase – ROS – NF-κB pathway and eNOS uncoupling.

Iduna protects HT22 cells from hydrogen peroxide-induced oxidative stress through interfering poly(ADP-ribose) polymerase-1-induced cell death (parthanatos)

2013 ◽  
Vol 25 (4) ◽  
pp. 1018-1026 ◽  
Author(s):  
Haoxiang Xu ◽  
Peng Luo ◽  
Yongbo Zhao ◽  
Mingming Zhao ◽  
Yuefan Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Ht22 Cells

Prior Increase in Metallothionein Levels is Required to Prevent Doxorubicin Cardiotoxicity1

2002 ◽  
Vol 227 (8) ◽  
pp. 652-657 ◽  
Author(s):  
Xiuhua Sun ◽  
Y. James Kang
Keyword(s):  
Oxidative Stress ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Tissue Injury ◽  
Morphological Changes ◽  
Oxidative Injury ◽  
Creatine Kinase Activity ◽  
Mouse Heart ◽  
Organ Systems ◽  
Heart Injury

Many studies have shown that metallothionein (MT) can be increased significantly by different oxidative insults in multiple organ systems. However, the increase in MT production often falls to protect against oxidative tissue injury. On the other hand, recent studies using a cardiac-specific, MT-overexpressing, transgenic mouse model have shown that MT protects against oxidative heart injury. Thus, the present study was undertaken to test the hypothesis that prior increase in MT levels is required to prevent oxidative injury. Oxidative heart injury was induced by doxorubicin (DOX), an important anticancer drug that causes severe cardiotoxicity through oxidative stress. Cardiac-specific, MT-overexpressing, transgenic mice and wild-type (WT) FVB mice were treated with OOX at 20 mg/kg. Four days after the treatment, MT concentrations were markedly elevated in the WT mouse heart. The elevated MT concentrations were comparable with those found in the transgenic mouse heart, which did not show further MT elevation in response to DOX challenge. Severe oxidative injury occurred in the heart of WT mice, including myocardial lipid peroxidation, morphological changes as examined by electron microscopy, high levels of serum creatine kinase activity, and decreased total glutathione concentrations in the heart. However, all of these pathological changes were significantly inhibited in the MT-transgenic mice. Therefore, this study demonstrates that there is a correlation between MT induction and oxidative stress in the DOX-treated mouse heart. However, MT can protect the heart from oxidative injury only if it is present prior to induction of oxidative stress.

scholarly journals Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells

2014 ◽  
Vol 34 (4) ◽  
pp. 1159-1168 ◽  
Author(s):  
SHU-HUI DAI ◽  
TAO CHEN ◽  
YU-HAI WANG ◽  
JIE ZHU ◽  
PENG LUO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Mitochondrial Function ◽  
Ht22 Cells

scholarly journals Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaojia Ni ◽  
Siu Ling Wong ◽  
Chi Ming Wong ◽  
Chi Wai Lau ◽  
Xiaogeng Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Isometric Tension ◽  
Protective Mechanism ◽  
Enos Expression ◽  
Isolated Rat

Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress.Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2∙-) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy.Results. ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reducedO2∙-accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2.Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP’s role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.

scholarly journals Peculiarities of the metabolic activity of mesenchimal stem cells under oxidative stress

2020 ◽  
Vol 26 ◽  
pp. 212-216
Author(s):  
M. V. Kovalchuk ◽  
N. S. Shuvalova ◽  
V. A. Kordium
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Metabolic Activity ◽  
Therapeutic Potential ◽  
Critical Concentration ◽  
Test Results ◽  
Standard Methods ◽  
Mtt Test

Aim. Oxidative stress is considered to be one of the major damaging factors that limits the therapeutic potential of mesenchymal stem cells (MSCs). The purpose of our work was to study the metabolic activity of Wharton jelly-derived MSC of different donor origin under oxidative stress conditions induced by hydrogen peroxide. Methods. MSC were obtained by the explant method and cultured according to standard methods. Oxidative stress was caused by treating cells with different concentrations of hydrogen peroxide. The metabolic activity of MSCs was evaluated using the MTT test. Results. Analysis of the MTT test showed a biphasic dependence of the MSC response to the concentration of H2O2. Concentrations of hydrogen peroxide from 6.25 to 50 μM increased the level of metabolic activity of MSCs, and concentrations from 50 to 440 μM inhibited metabolic activity. The maximum stimulating effect was observed at concentrations of 12.5 μM and 25 μM depending on the donor. Conclusions. The response of cells to oxidative stress corresponded to the hormetic dependence, and the points of critical concentration and maximum stimulation were individual for each donor. Processes such as preconditioning MSCs with hydrogen peroxide to increase their survival rate during transplantation also require personalization of the approach depending on the points of maximum stimulation. Keywords: mesenchymal stem cells, hydrogen peroxide, oxidative stress.

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