Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Polydatin protects neuronal cells from hydrogen peroxide damage by activating CREB/Ngb signaling

ABSTRACT: Oxidative stress-induced neuronal cell death contributes significantly to the physiological processes of a number of neurological disorders. Polydatin (PD) has been reported to protect against Alzheimer's disease (AD), ischemic stroke and traumatic brain injury. However, the underlying neuroprotective mechanisms remain to be elucidated. The current study suggested that PD activates AKT/cAMP response element-binding protein (CREB) signaling and induces neuroglobin (Ngb) to protect neuronal cells from hydrogen peroxide (H2O2) in vitro. PD inhibited the H2O2-induced neuronal cell death of primary mouse cortical neurons and N2a cells. Functional studies showed that PD attenuated H2O2-induced mitochondrial dysfunction and mitochondrial reactive oxygen species production. Mechanistically, PD was verified to induce the phosphorylation of AKT and CREB and increase the protein level of Ngb. The luciferase assay results showed that Ngb transcriptional activity was activated by CREB, especially after PD treatment. It was further indicated that PD increased the transcription of Ngb by enhancing the binding of CREB to the promoter region of Ngb. Finally, Ngb knockdown largely attenuated the neuroprotective role of PD against H2O2. The results indicated that PD protected neuronal cells from H2O2 by activating CREB/Ngb signaling in neuronal cells, indicating that PD has a neuroprotective effect against neurodegenerative diseases.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8600421 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Mitochondrial Ferritin Protects Hydrogen Peroxide-Induced Neuronal Cell Damage.

Project description:Oxidative stress and iron accumulation are tightly associated with neurodegenerative diseases. Mitochondrial ferritin (FtMt) is identified as an iron-storage protein located in the mitochondria, and its role in regulation of iron hemeostasis in neurodegenerative diseases has been reported. However, the role of FtMt in hydrogen peroxide (H2O2)-induced oxidative stress and iron accumulation in neuronal cells has not been studied. Here, we overexpressed FtMt in neuroblastoma SH-SY5Y cells and induced oxidative stress by treating with extracellular H2O2. We found that overexpression of FtMt significantly prevented cell death induced by H2O2, particularly the apoptosis-dependent cell death. The protective effects involved inhibiting the generation of cellular reactive oxygen species, sustaining mitochondrial membrane potential, maintaining the level of anti-apoptotic protein Bcl-2, and inhibiting the activation of pro-apoptotic protein caspase 3. We further explored the mechanism of these protective effects and found that FtMt expression markedly altered iron homeostasis of the H2O2 treated cells as compared to that of controls. The FtMt overexpression significantly reduced cellular labile iron pool (LIP) and protected H2O2-induced elevation on LIP. While in H2O2 treated SH-SY5Y cells, the increased iron uptake and reduced iron release, in correlation with levels of DMT1(-IRE) and ferroportin 1, resulted in heavy iron accumulation, the FtMt overexpressing cells didn't show any significant changes in levels of iron transport proteins and in the level of LIP. These results implicate a neuroprotective role of FtMt on H2O2-induced oxidative stress, which may provide insights into the treatment of iron accumulation associated neurodegenerative diseases.

| S-EPMC5524808 | biostudies-other

Chrysanthemum indicum Prevents Hydrogen Peroxide-Induced Neurotoxicity by Activating the TrkB/Akt Signaling Pathway in Hippocampal Neuronal Cells.

Project description:Oxidative stress-mediated neuronal damage is associated with the pathogenesis and development of neurodegenerative diseases. Chrysanthemum indicum has antioxidant properties. However, the neuroprotective effects and the cellular mechanism of C. indicum ethanol extract (CIE) against oxidative damage in hippocampal neuronal cells have not been clearly elucidated. Therefore, this study investigated whether CIE has protective effects against hydrogen peroxide (H2O2)-induced oxidative toxicity in HT22 cells. CIE pretreatment significantly improved neuronal cell viability. Moreover, the formation of intracellular reactive oxygen species and apoptotic bodies, and mitochondrial depolarization were significantly reduced in HT22 cells with H2O2-induced oxidative toxicity. Furthermore, CIE increased the phosphorylation of tropomyosin-related kinase receptor B (TrkB), protein kinase B (Akt), cAMP response element-binding protein, the expression of brain-derived neurotrophic factor, antioxidant enzymes, and the nuclear translocation of nuclear factor erythroid 2-related factor 2 by activating the TrkB/Akt signaling pathway. In contrast, the addition of K252a, a TrkB inhibitor, or MK-2206, an Akt-selective inhibitor, reduced the neuroprotective and antioxidant effects of CIE. Taken together; CIE exhibits neuroprotective and antioxidant effects against oxidative damage. Therefore, it can be a potential agent for treating oxidative stress-related neurodegenerative diseases.

| S-EPMC8618340 | biostudies-literature

Activation of the ERK/Creb/Bcl‑2 pathway protects periodontal ligament stem cells against hydrogen peroxide‑induced oxidative stress.

Project description:Periodontal ligament stem cells (PDLSCs) are promising stem cells sources for regenerative medicine, particularly clinical periodontal ligament repair. It is critical to maintain high quality and a large quantity of PDLSCs for clinical usage. However, how PDLSCs respond to environmental stimuli, including reactive oxygen species (ROS), is poorly understood. The aim of the present study was to investigate how PDLSCs react to oxidative stress and the underlying mechanisms. Hydrogen peroxide‑induced oxidative stress was used to mimic a ROS increase in rat PDLSCs. The expression levels of Creb were detected under oxidative stress to examine the role that Creb serves in PDLSCs under oxidative stress. The present results demonstrated that the expression of Creb was reduced in a dose‑dependent manner in response to the H2O2 stimulus. Overexpressing Creb significantly reduced the ROS levels and protein expression levels of apoptotic genes in PDLSCs. The phosphorylation of the ERK pathway is indispensable in the activation of Creb‑induced protection. Our results revealed a protective role of Creb in ROS‑induced apoptosis, and validated the ERK/Creb/apoptosis regulator Bcl‑2 pathway works as an anti‑apoptotic signaling in PDLSCs. These findings will facilitate the in vitro culturing of PDLSCs for clinical usage and promote stem cell based therapy for periodontal tissue regeneration.

| S-EPMC6472112 | biostudies-literature

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2.

Project description:Oxidative damage is a major cause of lung diseases, including pulmonary fibrosis. Laminarin is a kind of polysaccharide extracted from brown algae and plays vital roles in various biological processes. However, the functions and mechanisms of laminarin in pulmonary oxidative damage are poorly understood. This study aimed at investigating the protective effect of laminarin against pulmonary oxidative damage and underlying mechanisms. Human lung fibroblasts MRC-5 cells were treated with hydrogen peroxide to induce oxidative damage. Laminarin treatment was performed before or after hydrogen peroxide treatment, and then major indexes of oxidative damage, including superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT), were quantified by biochemical assays. The expression of oxidation-related factor, nuclear factor erythroid 2 like 2 (NRF2) was analyzed by qPCR, Western blot and immunofluorescence assay. NRF2 knockdown and overexpression were performed by cell transfection to reveal possible mechanisms. Results showed that laminarin treatment of 0.020 mg/mL for 24 h, especially the pre-treatment, could significantly relieve changes in SOD, MDA, GSH and CAT that were altered by hydrogen peroxide, and promote NRF2 mRNA (P < 0.001). NRF2 protein was also elevated by laminarin, and nuclear translocation was observed. Factors in NRF2 signaling pathways, including KEAP1, NQO1, GCLC and HO1, were all regulated by laminarin. Roles of NRF2 were tested, suggesting that NRF2 regulated the concentration of SOD, MDA, GSH and CAT, suppressed KEAP1, and promoted NQO1, GCLC and HO1. These findings suggested the protective role of laminarin against pulmonary oxidative damage, which might involve the regulation of NRF2 signaling pathways. This study provided information for the clinical application of laminarin to pulmonary diseases like pulmonary fibrosis.

| S-EPMC5541921 | biostudies-literature

Four-octyl itaconate activates Keap1-Nrf2 signaling to protect neuronal cells from hydrogen peroxide.

Project description:BackgroundFour-octyl itaconate (OI), the itaconate's cell-permeable derivative, can activate Nrf2 signaling via alkylation of Keap1 at its cysteine residues. The current study tested the potential neuroprotective function of OI in hydrogen peroxide (H2O2)-treated neuronal cells.MethodsSH-SY5Y neuronal cells and epigenetically de-repressed (by TSA treatment) primary murine neurons were treated with OI and/or H2O2. Nrf2 pathway genes were examined by Western blotting assay and real-time quantitative PCR analysis. Neuronal cell death was tested by the LDH and trypan blue staining assays. Apoptosis was tested by TUNEL and Annexin V assays.ResultsIn SH-SY5Y neuronal cells and primary murine neurons, OI activated Nrf2 signaling, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation, as well as expression of Nrf2-regulated genes (HO1, NQO1 and GCLC) and ninjurin2 (Ninj2). Functional studies showed that OI attenuated H2O2-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage as well as neuronal cell death and apoptosis. shRNA-mediated knockdown, or CRISPR/Cas9-induced knockout of Nrf2 almost abolished OI-induced neuroprotection against H2O2. Keap1 is the primary target of OI. Keap1 knockout by CRISPR/Cas9 method mimicked and abolished OI-induced actions in SH-SY5Y cells. Introduction of a Cys151S mutant Keap1 in SH-SY5Y cells reversed OI-induced Nrf2 activation and anti-H2O2 neuroprotection.ConclusionsOI activates Keap1-Nrf2 signaling to protect SH-SY5Y cells and epigenetically de-repressed primary neurons from H2O2 in vitro.

| S-EPMC6238317 | biostudies-literature

Polyphenol-rich strawberry extract protects human dermal fibroblasts against hydrogen peroxide oxidative damage and improves mitochondrial functionality.

Project description:Strawberry bioactive compounds are widely known to be powerful antioxidants. In this study, the antioxidant and anti-aging activities of a polyphenol-rich strawberry extract were evaluated using human dermal fibroblasts exposed to H2O2. Firstly, the phenol and flavonoid contents of strawberry extract were studied, as well as the antioxidant capacity. HPLC-DAD analysis was performed to determine the vitamin C and β-carotene concentration, while HPLC-DAD/ESI-MS analysis was used for anthocyanin identification. Strawberry extract presented a high antioxidant capacity, and a relevant concentration of vitamins and phenolics. Pelargonidin- and cyanidin-glycosides were the most representative anthocyanin components of the fruits. Fibroblasts incubated with strawberry extract and stressed with H2O2 showed an increase in cell viability, a smaller intracellular amount of ROS, and a reduction of membrane lipid peroxidation and DNA damage. Strawberry extract was also able to improve mitochondrial functionality, increasing the basal respiration of mitochondria and to promote a regenerative capacity of cells after exposure to pro-oxidant stimuli. These findings confirm that strawberries possess antioxidant properties and provide new insights into the beneficial role of strawberry bioactive compounds on protecting skin from oxidative stress and aging.

| S-EPMC6270910 | biostudies-literature

Ciclopirox protects mitochondria from hydrogen peroxide toxicity.

Project description:1 The mitochondrial respiratory chain produces reactive oxygen species (ROS) during normal electron transport. Despite producing ROS, mitochondria are vulnerable to oxidative stress. Mitochondrial dysfunction has been associated with many degenerative diseases, making it important to identify compounds that protect mitochondria from ROS-mediated toxicity. Here we report that ciclopirox (CPX) blocks H2O2-induced mitochondrial injury by maintaining mitochondrial transmembrane potential (Deltapsim). 2 CPX completely blocked H2O2-stimulated release of lactate dehydrogenase (a marker of cell death) and decrease in MTT reduction (a marker of mitochondrial function) in adenocarcinoma SK-HEP-1 cells. 3 H2O2 rapidly depolarized the Deltapsim, and CPX blocked this H2O2-stimulated Deltapsim decrease. Similar data were obtained in experiments using mitochondria isolated from rat liver. 4 Furthermore, CPX effectively inhibited H2O2-induced mitochondrial permeability transition pore (MPTP) opening. In de-energized mitochondria, however, CPX did not inhibit Ca2+-evoked MPTP opening, indicating that CPX is not a direct inhibitor of the MPTP. 5 Oxygen consumption studies showed that in the presence of pyruvate and malate CPX restored the rate of state 3 to state 4 respiration decreased by H2O2. Consistent with this, CPX replenished ATP levels lowered by H2O2. 6 The present results indicate that CPX protects SK-HEP-1 cells from H2O2 cytotoxicity by inhibiting Deltapsim decrease and indirectly preventing MPTP opening.

| S-EPMC1576158 | biostudies-other

Cytoprotective propensity of Bacopa monniera against hydrogen peroxide induced oxidative damage in neuronal and lung epithelial cells.

Project description:Hydrogen peroxide (H2O2), a major reactive oxygen species (ROS) produced during oxidative stress, is toxic to the cells. Hence, H2O2 has been extensively used to study the effects of antioxidant and cytoprotective role of phytochemicals. In the present investigation H2O2 was used to induce oxidative stress via ROS production within PC12 and L132 cells. Cytoprotective propensity of Bacopa monniera extract (BME) was confirmed by cell viability assays, ROS estimation, lipid peroxidation, mitochondria membrane potential assay, comet assay followed by gene expression studies of antioxidant enzymes in PC12 and L132 cells treated with H2O2 for 24 h with or without BME pre-treatment. Our results elucidate that BME possesses radical scavenging activity by scavenging 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), superoxide radical, and nitric oxide radicals. The IC50 value of BME against these radicals was found to be 226.19, 15.17, 30.07, and 34.55 µg/ml, respectively). The IC50 of BME against ROS, lipid peroxidation and protein carbonylation was found to be 1296.53, 753.22, and 589.04 µg/ml in brain and 1137.08, 1079.65, and 11101.25 µg/ml in lung tissues, respectively. Further cytoprotective potency of the BME ameliorated the mitochondrial and plasma membrane damage induced by H2O2 as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase leakage assays in both PC12 and L132 cells. H2O2 induced cellular, nuclear and mitochondrial membrane damage was restored by BME pre-treatment. H2O2 induced depleted antioxidant status was also replenished by BME pre-treatment. This was confirmed by spectrophotometric analysis, semi-quantitative RT-PCR and western blot studies. These results justify the traditional usage of BME based on its promising antioxidant and cytoprotective property.

| S-EPMC4698260 | biostudies-literature

Dual Oxidase, a Hydrogen-Peroxide-Producing Enzyme, Regulates Neuronal Oxidative Damage and Animal Lifespan in <i>Drosophila melanogaster</i>.

Project description:Reducing the oxidative stress in neurons extends lifespan in Drosophila melanogaster, highlighting the crucial role of neuronal oxidative damage in lifespan determination. However, the source of the reactive oxygen species (ROS) that provoke oxidative stress in neurons is not clearly defined. Here, we identify dual oxidase (duox), a calcium-activated ROS-producing enzyme, as a lifespan determinant. Due to the lethality of duox homozygous mutants, we employed a duox heterozygote that exhibited normal appearance and movement. We found that duox heterozygous male flies, which were isogenized with control flies, demonstrated extended lifespan. Neuronal knockdown experiments further suggested that duox is crucial to oxidative stress in neurons. Our findings suggest duox to be a source of neuronal oxidative stress associated with animal lifespan.

| S-EPMC9265666 | biostudies-literature

Quantitative biology of hydrogen peroxide signaling.

Project description:Hydrogen peroxide (H2O2) controls signaling pathways in cells by oxidative modulation of the activity of redox sensitive proteins denominated redox switches. Here, quantitative biology concepts are applied to review how H2O2 fulfills a key role in information transmission. Equations described lay the foundation of H2O2 signaling, give new insights on H2O2 signaling mechanisms, and help to learn new information from common redox signaling experiments. A key characteristic of H2O2 signaling is that the ratio between reduction and oxidation of redox switches determines the range of H2O2 concentrations to which they respond. Thus, a redox switch with low H2O2-dependent oxidability and slow reduction rate responds to the same range of H2O2 concentrations as a redox switch with high H2O2-dependent oxidability, but that is rapidly reduced. Yet, in the first case the response time is slow while in the second case is rapid. H2O2 sensing and transmission of information can be done directly or by complex mechanisms in which oxidation is relayed between proteins before oxidizing the final regulatory redox target. In spite of being a very simple molecule, H2O2 has a key role in cellular signaling, with the reliability of the information transmitted depending on the inherent chemical reactivity of redox switches, on the presence of localized H2O2 pools, and on the molecular recognition between redox switches and their partners.

| S-EPMC5436100 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data