scholarly journals Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway

2013 ◽  
Vol 169 (5) ◽  
pp. 1058-1071 ◽  
Author(s):  
Wen-Yu Wu ◽  
Wen-Yi Wang ◽  
Yan-Ling Ma ◽  
Hong Yan ◽  
Xin-Bo Wang ◽  
...  
Keyword(s):  
Glucose Deprivation ◽  
Cardiomyocyte Apoptosis ◽  
Tanshinone Iia ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α

scholarly journals Upregulation of miR-216a exerts neuroprotective effects against ischemic injury through negatively regulating JAK2/STAT3-involved apoptosis and inflammatory pathways

2019 ◽  
Vol 130 (3) ◽  
pp. 977-988 ◽  
Author(s):  
Yu Shuang Tian ◽  
Di Zhong ◽  
Qing Qing Liu ◽  
Xiu Li Zhao ◽  
Hong Xue Sun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Mediators ◽  
Neurological Deficit ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Luciferase Assay ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α

OBJECTIVEIschemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke–related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke.METHODSThe JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)–treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)–induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3′ untranslated region (3′UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase–9 [MMP-9], tumor necrosis factor–α [TNF-α], and interleukin-1β [IL-1β]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V–FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits.RESULTSJAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3′UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1β). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit.CONCLUSIONSThese findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.

scholarly journals Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-κB signaling

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Mouli Tian ◽  
Mei Yang ◽  
Zhenjie Li ◽  
Yiru Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins

Abstract We aimed to investigate the anti-inflammatory role of fluoxetine, a selective serotonin reuptake inhibitor, in microglia (MG) and the mechanisms under oxygen glucose deprivation/reoxygenation (OGD/R). An OGD/R model on BV-2 cells was used for the study of microglia under ischemia/reperfusion injury in ischemic stroke. Lentiviral transfection was applied to knock down IκB-α. Enzyme-linked immunosorbent assay (ELISA) was used for detecting levels of TNF-α, IL-1β, and IL-6, and real-time PCR was used to assess the expression of IκB-α protein. Western blotting was applied to analyze NF-κB-signaling related proteins and Cell Counting Kit-8 (CCK-8) was used for assessing cell viability. Molecular docking and drug affinity responsive target stability (DARTS) assay were used for the detection of the interaction between IκB-α and fluoxetine. We found that fluoxetine decreased the levels of TNF-α, IL-1β, and IL-6 in supernatant as well as NF-κB subunits p65 and p50 in BV-2 cells under OGD/R. Fluoxetine significantly increased the level of IκB-α through the inhibition of IκB-α ubiquitylation and promoted the bonding of IκB-α and fluoxetine in BV-2 cells under OGD/R. Knocking down IκB-α attenuated the decreasing effect of TNF-α, IL-1β, and IL-6 as well as p65 and p50 in BV-2 cells under OGD/R led to by fluoxetine. In conclusion, our present study demonstrated the anti-inflammatory role of fluoxetine and its mechanisms related to the modulation of NF-κB-related signaling in MG under ischemia/reperfusion challenge.

scholarly journals Ginsenoside Rc Protects Neurons From Oxygen-glucose Deprivation Injuries and Its Mechanistic Investigation via a Network Pharmacology-based Analysis

2020 ◽  
Author(s):  
Mingmin Huang ◽  
Shaoru Chen ◽  
Kening Zheng ◽  
Qu Liu ◽  
Kening Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Viability ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Network Pharmacology ◽  
Oxygen Glucose Deprivation ◽  
Cell Toxicity ◽  
Tnf Α ◽  
Neuron Damage ◽  
Ginsenoside Rc

Abstract Background: Ginsenoside Rc (Rc) is one of the major active components of Panax ginseng Meyer. Studies have shown that Rc has remarkable effect in protection of nervous system. However, the potential molecular mechanism of its neuroprotective effect remains unclear. Our study aim to investigate the neuroprotective effect of Rc on neuron damage and explore the potential mechanism on its regulation of TNF-α and DRP-1.Methods: Oxygen-glucose deprivation reperfusion (OGD/R) cell neuron damage modle was induced by Na2S2O4 and EBSS solution. After preventive administration, cell viability and cell toxicity were detected to evaluate the putative neuroprotective properties of Rc. Network pharmacology and molecular docking simulation studies were performed to predict the potential targets and pharmacological mechanism. Furthermore, the prediction was validated via western blot assay and specific antagonist. Results: In OGD/R injured cells, Rc significantly improved cell viability (Rc middle dose vs. OGD/R model: 67.3±2.33% vs. 55.7±1.14%, P<0.05) and obviously decreased cell toxicity (Rc middle dose vs. OGD/R model: 147±39.7% vs. 232±29.4%, P<0.01). Analysis of network pharmacology and molecular docking indicated that the key targets of Rc are TNF-α and DRP-1. Subsequently molecular biological studies showed a significant increase on expression of TNF-α and DRP-1 in model group. Conversely, administration of Rc reversed the alteration significantly and presented a dose dependence. By adding antagonist, we validated that Rc had an indirect regulation on TNF-α and DRP-1. Conclusions: Rc possess protective properties against OGD-induced neuron damage by regulating the expression of TNF-α and DRP-1.

scholarly journals TACE/ADAM17–TNF-α Pathway in Rat Cortical Cultures after Exposure to Oxygen–Glucose Deprivation or Glutamate

2002 ◽  
Vol 22 (5) ◽  
pp. 576-585 ◽  
Author(s):  
Olivia Hurtado ◽  
Ignacio Lizasoain ◽  
Paz Fernández-Tomé ◽  
Alberto Álvarez-Barrientos ◽  
Juan C. Leza ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucose Deprivation ◽  
Microglial Cells ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Cortical Cultures ◽  
Rat Forebrain ◽  
Necrosis Factor ◽  
Mixed Cortical Cultures

The role of the tumor necrosis factor (TNF)-α convertase (TACE/ADAM17) in the adult nervous system remains poorly understood. The authors have previously demonstrated that TACE is upregulated in rat forebrain slices exposed to oxygen–glucose deprivation (OGD). They have now used rat mixed cortical cultures exposed to OGD or glutamate to study (1) TACE expression and localization, and (2) the effects of TNF-α release on cell viability. OGD- or glutamate-caused TNF-α release, an effect that was blocked by the TACE inhibitor BB3103 (BB) (0.1–1 μmol/L; control: 1.67 ± 0.59; OGD: 6.59 ± 1.52; glutamate: 3.38 ± 0.66; OGD ± BB0.1: 3.23 ± 0.67; OGD ± BB1: 1.33 ± 0.22 pg/mL, n = 6, P < 0.05). Assay of TACE activity as well as Western blot showed that TACE expression is increased in OGD- or glutamate-exposed cells. In control cultures, TACE immunoreactivity was present in some microglial cells, whereas, after OGD or glutamate, TACE immunostaining appeared in most microglial cells and in some astrocytes. Conversely, BB3103 (0.1 μmol/L) caused apoptosis after glutamate exposure as shown by annexin and Hoechst 33342 staining and caspase-3 activity, an effect mimicked by the proteasome inhibitor MG-132 (caspase activity: glutamate: 5.1 ± 0.1; glutamate + BB: 7.8 ± 0.8; glutamate + MG: 11.9 ± 0.5 pmol · min−1 mg−1 protein, n = 4, P < 0.05), suggesting that translocation of the transcription factor NF-κB mediates TNF-α–induced antiapoptotic effect. Taken together, these data demonstrate that, in rat mixed neuronal–glial cortical cultures exposed to OGD or glutamate, (1) TACE/ADAM17 activity accounts for the majority of TNF-α shedding, (2) an increase in glial TACE expression contributes to the rise in TNF-α, and (3) TNF-α release in this setting inhibits apoptosis via activation of the transcription factor NF-κB.

Up-regulation of TNF-α convertase (TACE/ADAM17) after oxygen–glucose deprivation in rat forebrain slices

2001 ◽  
Vol 40 (8) ◽  
pp. 1094-1102 ◽  
Author(s):  
Olivia Hurtado ◽  
Antonio Cárdenas ◽  
Ignacio Lizasoain ◽  
Lisardo Boscá ◽  
Juan C Leza ◽  
...  
Keyword(s):  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Tnf Α ◽  
Rat Forebrain

scholarly journals Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

2017 ◽  
Vol 42 (3) ◽  
pp. 987-998 ◽  
Author(s):  
Ruixue Xia ◽  
Chunxue Ji ◽  
Leguo Zhang
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Cell Activity ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Neuroprotective Effects ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Rat Astrocytes ◽  
Related Proteins

Backgrounds/Aims: Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. In this study, we investigated the effects of PYC on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary rat astrocytes. Methods: The primary rat astrocytes were randomly divided into 6 groups, blank control, OGD/R, OGD/R+PYC (10, 20, 40, and 60 µg/mL). The cell activity were detected by MTT and LDH assays, then the levels of oxidant products [malondialdehyde (MDA) and reactive oxygen species (ROS)] , antioxidants [superoxide dismutase (SOD)], mitochondrial membrane potential (MMP) and inflammatory cytokines were detected. In addition, the expression levels of apoptosis-related proteins (Bax, Bcl-2 and Cleaved caspase 3), proinflammatory factors (NF-κB p65), and p-ERK1/2 were measured by Western blot analysis. Results: The results showed that PYC incubation dose-dependently attenuated cell viability loss, LDH leakage, oxidative stress, inflammatory cytokines accumulation and cell apoptosis caused by OGD/R. Furthermore, PYC pretreatment dose-dependently suppressed OGD/R-induced NF-κB p65 nuclear translocation, NF-κB activity and ERK1/2 phosphorylation. Similarly to PYC, NF-κB inhibitor PDTC and ERK1/2 inhibitor PD098059 dramatically inhibited OGD/R-induced NF-κB activation, ERK1/2 phosphorylation, and ROS production, as well as TNF-α secretion. Conclusions: These findings revealed that PYC has neuroprotective effects against OGD/R-induced injury via NF-κB and ERK1/2 pathways in primary rat astrocytes.

scholarly journals AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation

Oncotarget ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 4511-4521 ◽  
Author(s):  
Yingfeng Weng ◽  
Jixian Lin ◽  
Hui Liu ◽  
Hui Wu ◽  
Zhimin Yan ◽  
...  
Keyword(s):  
Neuronal Cells ◽  
Glucose Deprivation ◽  
Tanshinone Iia ◽  
Oxygen Glucose Deprivation ◽  
Ampk Activation

scholarly journals LncRNA Chaer Prevents Cardiomyocyte Apoptosis From Acute Myocardial Infarction Through AMPK Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiyu He ◽  
Xiaojun Zeng ◽  
Deke Zhou ◽  
Peiying Liu ◽  
Dunzheng Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Heart Function ◽  
Glucose Deprivation ◽  
Cardiomyocyte Apoptosis ◽  
Oxygen Glucose Deprivation ◽  
Compound C ◽  
Life Threatening

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro, overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo, forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI.

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