scholarly journals Arctic Ground Squirrel (Spermophilus Parryii) Hippocampal Neurons Tolerate Prolonged Oxygen—Glucose Deprivation and Maintain Baseline ERK1/2 and JNK Activation Despite Drastic ATP Loss

2008 ◽  
Vol 28 (7) ◽  
pp. 1307-1319 ◽  
Author(s):  
Sherri L Christian ◽  
Austin P Ross ◽  
Huiwen W Zhao ◽  
Heidi J Kristenson ◽  
Xinhua Zhan ◽  
...  
Keyword(s):  
Cell Death ◽  
Hippocampal Slices ◽  
Glucose Deprivation ◽  
Mapk Signaling ◽  
Ground Squirrels ◽  
Atp Depletion ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Glucose Deprivation ◽  
Acute Hippocampal Slices ◽  
Jnk Activation

Oxygen—glucose deprivation (OGD) initiates a cascade of intracellular responses that culminates in cell death in sensitive species. Neurons from Arctic ground squirrels (AGS), a hibernating species, tolerate OGD in vitro and global ischemia in vivo independent of temperature or torpor. Regulation of energy stores and activation of mitogen-activated protein kinase (MAPK) signaling pathways can regulate neuronal survival. We used acute hippocampal slices to investigate the role of ATP stores and extracellular signal-regulated kinase (ERK)1/2 and Jun NH2-terminal kinase (JNK) MAPKs in promoting survival. Acute hippocampal slices from AGS tolerated 30 mins of OGD and showed a small but significant increase in cell death with 2 h OGD at 37 C. This tolerance is independent of hibernation state or season. Neurons from AGS survive OGD despite rapid ATP depletion by 3 mins in interbout euthermic AGS and 10 mins in hibernating AGS. Oxygen—glucose deprivation does not induce JNK activation in AGS and baseline ERK1/2 and JNK activation is maintained even after drastic depletion of ATP. Surprisingly, inhibition of ERK1/2 or JNK during OGD had no effect on survival, whereas inhibition of JNK increased cell death during normoxia. Thus, protective mechanisms promoting tolerance to OGD by AGS are downstream from ATP loss and are independent of hibernation state or season.

miR-666-3p mediates the protective effects of mesenchymal stem cell-derived exosomes against oxygen–glucose deprivation and reoxygenation-induced cell injury in brain microvascular endothelial cells via mitogen-activated protein kinase pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Li-yun Kong ◽  
Yan Li ◽  
Ding-yu Rao ◽  
Bing Wu ◽  
Cheng-peng Sang ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Glucose Deprivation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Assay ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
Mitogen Activated Protein

Background: Previous studies have reported that mesenchymal stem cell (MSC)-derived exosomes can protect rat primary brain microvascular endothelial cells (BMECs) against oxygen–glucose deprivation and reoxygenation (OGD/R)-induced injury. Objective: To identify the key factors mediating the protective effects of MSC-derived exosomes. Methods: Rat primary BMECs were either pretreated or not pretreated with MSC-derived exosomes before exposure to OGD/R. Naïve cells were used as a control. After performing small RNA deep sequencing, quantitative reverse transcription polymerase chain reaction was performed to validate microRNA (miRNA) expression. The effects of rno-miR-666-3p on cell viability, apoptosis, and inflammation in OGD/R-exposed cells were assessed by performing the Cell Counting Kit 8 assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Moreover, the role of rno-miR-666-3p in regulating gene expression in OGD/R-exposed cells was studied using mRNA deep sequencing. Lastly, to evaluate whether mitogen-activated protein kinase 1 (MAPK1) was the target of rno-miR-666-3p, western blotting and the dual-luciferase assay were performed. Results: MSC-derived exosomes altered the miRNA expression patterns in OGD/R-exposed BMECs. In particular, the expression levels of rno-miR-666-3p, rno-miR-92a-2-5p, and rno-miR-219a-2-3p decreased in OGD/R-exposed cells compared with those in the control; however, MSC-derived exosomes restored the expression levels of these miRNAs under OGD/R conditions. rno-miR-666-3p overexpression enhanced cell viability and alleviated the apoptosis of OGD/R-exposed cells. Moreover, rno-miR-666-3p suppressed OGD/R-induced inflammation. mRNA deep sequencing revealed that rno-miR-666-3p is closely associated with the MAPK signaling pathway. Western blotting and the dual-luciferase assay confirmed that MAPK1 is the target of rno-miR-666-3p. Conclusion: MSC-derived exosomes restore rno-miR-666-3p expression in OGD/R-exposed BMECs. Moreover, this specific miRNA exerts protective effects against OGD/R by suppressing the MAPK signaling pathway.

scholarly journals Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Shu Xu ◽  
Ya Li ◽  
Ju-ping Chen ◽  
Da-Zhuang Li ◽  
Qin Jiang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Apoptosis ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Glucose Deprivation ◽  
Non Coding Rna ◽  
Mitogen Activated Protein ◽  
Long Non Coding Rna

Abstract Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. In SH-SY5Y cells and primary murine neurons, we report that OGD/R induces the accumulation of the microRNA miR-422a, leading to downregulation of miR-422a targets myocyte enhancer factor-2D (MEF2D) and mitogen-activated protein kinase kinase 6 (MAPKK6). Ectopic miR-422a inhibition attenuated OGD/R-induced cell death and apoptosis, whereas overexpression of miR-422a induced significant neuronal cell apoptosis. In addition, OGD/R decreased the expression of the long non-coding RNA D63785 (Lnc-D63785) to regulate miR-422a accumulation. Lnc-D63785 directly associated with miR-422a and overexpression of Lnc-D63785 reversed OGD/R-induced miR-422a accumulation and neuronal cell death. OGD/R downregulated Lnc-D63785 expression through increased methyltransferase-like protein 3 (METTL3)-dependent Lnc-D63785 m6A methylation. Conversely METTL3 shRNA reversed OGD/R-induced Lnc-D63785 m6A methylation to decrease miR-422a accumulation. Together, Lnc-D63785 m6A methylation by OGD/R causes miR-422a accumulation and neuronal cell apoptosis.

scholarly journals Protective effect of 20-HETE inhibition in a model of oxygen-glucose deprivation in hippocampal slice cultures

2012 ◽  
Vol 302 (6) ◽  
pp. H1285-H1293 ◽  
Author(s):  
Marija Renic ◽  
Suresh N. Kumar ◽  
Debebe Gebremedhin ◽  
Matthew A. Florence ◽  
Nashaat Z. Gerges ◽  
...  
Keyword(s):  
Cell Death ◽  
Protective Effect ◽  
Caspase 3 ◽  
Hippocampal Slice ◽  
Hippocampal Slices ◽  
Glucose Deprivation ◽  
Dienoic Acid ◽  
Oxygen Glucose Deprivation ◽  
Iodide Uptake ◽  
Hippocampal Slice Cultures

Recent studies have indicated that inhibitors of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) may have direct neuroprotective actions since they reduce infarct volume after ischemia reperfusion in the brain without altering blood flow. To explore this possibility, the present study used organotypic hippocampal slice cultures subjected to oxygen-glucose deprivation (OGD) and reoxygenation to examine whether 20-HETE is released by organotypic hippocampal slices after OGD and whether it contributes to neuronal death through the generation of ROS and activation of caspase-3. The production of 20-HETE increased twofold after OGD and reoxygenation. Blockade of the synthesis of 20-HETE with N-hydroxy- N′-(4-butyl-2-methylphenol)formamidine (HET0016) or its actions with a 20-HETE antagonist, 20-hydroxyeicosa-6( Z),15( Z)-dienoic acid, reduced cell death, as measured by the release of lactate dehydrogenase and propidium iodide uptake. Administration of a 20-HETE mimetic, 20-hydroxyeicosa-5( Z),14( Z)-dienoic acid (5,14-20-HEDE), had the opposite effect and increased injury after OGD. The death of neurons after OGD was associated with an increase in the production of ROS and activation of caspase-3. These effects were attenuated by HET0016 and potentiated after the administration of 5,14-20-HEDE. These findings indicate that the production of 20-HETE by hippocampal slices is increased after OGD and that inhibitors of the synthesis or actions of 20-HETE protect neurons from ischemic cell death. The protective effect of 20-HETE inhibitors is associated with a decrease in superoxide production and activation of caspase-3.

scholarly journals Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response Against Oxygen-Glucose Deprivation- and Reoxygenation Treatments in an In Vitro Study

2016 ◽  
Vol 38 (4) ◽  
pp. 1472-1482 ◽  
Author(s):  
Xuelian Yang ◽  
Tetsuya Asakawa ◽  
Sha Han ◽  
Ling Liu ◽  
Wei Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Western Blot ◽  
Neuronal Apoptosis ◽  
Neuronal Survival ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Glucose Deprivation ◽  
Ldh Release

Background/Aims: Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS). Methods: Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH) release were measured in cultured neurons. Furthermore, the levels of IL-1β and nitric oxide (NO) release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis. Results: NSP administration can reverse abnormal variations in neurons and microglia-mediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1β and NO were significantly reduced by NSP in microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP. Conclusion: These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling pathways might play a potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.

scholarly journals Tumor Necrosis Factor Receptor-1 is Essential for LPS-Induced Sensitization and Tolerance to Oxygen—Glucose Deprivation in Murine Neonatal Organotypic Hippocampal Slices

2008 ◽  
Vol 29 (1) ◽  
pp. 73-86 ◽  
Author(s):  
Tina Markus ◽  
Tobias Cronberg ◽  
Corrado Cilio ◽  
Cornelis Pronk ◽  
Tadeusz Wieloch ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Hippocampal Slices ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Time Interval ◽  
Necrosis Factor

Inflammation and ischemia have a synergistic damaging effect in the immature brain. The role of tumor necrosis factor (TNF) receptors 1 and 2 in lipopolysaccharide (LPS)-induced sensitization and tolerance to oxygen—glucose deprivation (OGD) was evaluated in neonatal murine hippocampal organotypic slices. Hippocampal slices from balb/c, C57BL/6 TNFR1−/-, TNFR2−/-, and wild-type (WT) mice obtained at P6 were grown in vitro for 9 days. Preexposure to LPS immediately before OGD increased propidium iodide-determined cell death in regions CA1, CA3, and dentate gyrus from 4 up to 48 h after OGD ( P < 0.001). Extending the time interval between LPS exposure and OGD to 72 h resulted in tolerance, that is reduced neuronal cell death after OGD ( P < 0.05). Slices from TNFR1−/- mice showed neither LPS-induced sensitization nor LPS-induced tolerance to OGD, whereas both effects were present in slices from TNFR2−/- and WT mice. Cytokine secretion (TNFα and interleukin-6) during LPS exposure was decreased in TNFR1−/- slices and increased in TNFR2−/- as compared with WT slices. We conclude that LPS induces sensitization or tolerance to OGD depending on the time interval between exposure to LPS and OGD in murine hippocampal slice cultures. Both paradigms are dependent on signaling through TNFR1.

scholarly journals Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 923
Author(s):  
Yuan Yuan ◽  
Yanyu Zhai ◽  
Jingjiong Chen ◽  
Xiaofeng Xu ◽  
Hongmei Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Antioxidant Capacity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

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