scholarly journals Astragaloside and/or Hydroxysafflor Yellow A Attenuates Oxygen-Glucose Deprivation-Induced Cultured Brain Microvessel Endothelial Cell Death through Downregulation of PHLPP-1

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jinyi Cao ◽  
Kai Wang ◽  
Lu Lei ◽  
Lu Bai ◽  
Ruimin Liang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Migration And Invasion ◽  
Oxygen Glucose Deprivation ◽  
Traditional Chinese Medicines ◽  
Hydroxysafflor Yellow A ◽  
Chinese Medicines

The incidence of ischemic stroke, a life-threatening condition in humans, amongst Asians is high and the prognosis is poor. In the absence of effective therapeutics, traditional Chinese medicines have been used that have shown promising results. It is crucial to identify traditional Chinese medicine formulas that protect the blood-brain barrier, which is damaged by an ischemic stroke. In this study, we aimed to elucidate such formulas. Brain microvascular endothelial cells (BMECs) were used to establish an in vitro ischemia-reperfusion model for oxygen-glucose deprivation (OGD) experiments to evaluate the function of two traditional Chinese medicines, namely, astragaloside (AS-IV) and hydroxysafflor yellow A (HSYA), in protecting against BMEC. Our results revealed that AS-IV and HSYA attenuated the cell loss caused by OGD by increasing cell proliferation and inhibiting cell apoptosis. In addition, these compounds promoted the migration and invasion of BMECs in vitro. Furthermore, we found that BMECs rescued by AS-IV and HSYA could be functionally activated in vitro, with AS-IV and HSYA showing synergetic effects in rescuing BMECs survival in vitro by reducing the expression of PHLPP-1 and activating Akt signaling. Our results elucidated the potential of AS-IV and HSYA in the prevention and treatment of stroke by protecting against cerebral ischemia-reperfusion injury.

scholarly journals Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

2018 ◽  
Vol 50 (2) ◽  
pp. 783-797 ◽  
Author(s):  
Xianzhang Zeng ◽  
Hongliang Ren ◽  
Yana Zhu ◽  
Ruru Zhang ◽  
Xinxin Xue ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Ischemia Reperfusion ◽  
Survival Rates ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Sirna Transfection ◽  
Culture Model

Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX2 (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91phoxsiRNA. Conclusion: Knockdown of gp91phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model.

scholarly journals Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jiayu Tang ◽  
Zhiping Hu ◽  
Jieqiong Tan ◽  
Sonlin Yang ◽  
Liuwang Zeng
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Ubiquitin Proteasome System ◽  
Oxygen Glucose Deprivation ◽  
Protective Effects

Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders.

scholarly journals Cardioprotective Effect of Propofol against Oxygen Glucose Deprivation and Reperfusion Injury in H9c2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Dandan Zhao ◽  
Qing Li ◽  
Qiuping Huang ◽  
Xuguang Li ◽  
Min Yin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Underlying Mechanism ◽  
Oxygen Glucose Deprivation ◽  
H9c2 Cell ◽  
Dependent Manner ◽  
H9c2 Cells

Background. The intravenous anesthetic propofol is reported to be a cardioprotective agent against ischemic-reperfusion injury in the heart. However, the regulatory mechanism still remains unclear.Methods. In this study, we used H9c2 cell line under condition of oxygen glucose deprivation (OGD) followed by reperfusion (OGD/R) to inducein vitrocardiomyocytes ischemia-reperfusion injury. Propofol (5, 10, and 20 μM) was added to the cell cultures before and during the OGD/R phases to investigate the underlying mechanism.Results. Our data showed that OGD/R decreased cell viability, and increased lactate dehydrogenase leakage, and reactive oxygen species and malondialdehyde production in H9c2 cells, all of which were significantly reversed by propofol. Moreover, we found that propofol increased both the activities and protein expressions of superoxide dismutase and catalase. In addition, propofol increased FoxO1 expression in a dose-dependent manner and inhibited p-AMPK formation significantly.Conclusions. These results indicate that the propofol might exert its antioxidative effect through FoxO1 in H9c2 cells, and it has a potential therapeutic effect on cardiac disorders involved in oxidative stress.

scholarly journals Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability

2020 ◽  
Vol 11 ◽  
Author(s):  
Tiantian Wang ◽  
Chunxia Liu ◽  
Ling-hui Pan ◽  
Zhen Liu ◽  
Chang-long Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Endothelial Barrier ◽  
Oxygen Glucose Deprivation

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro.Methods: Sprague–Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood–air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence.Results:In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood–air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction.Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood–air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.

scholarly journals GRP78 Promotes Neural Stem Cell Antiapoptosis and Survival in Response to Oxygen-Glucose Deprivation (OGD)/Reoxygenation through PI3K/Akt, ERK1/2, and NF-κB/p65 Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Qian Liu ◽  
Yun Li ◽  
Lin Zhou ◽  
Yunzi Li ◽  
Pengfei Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Neural Cells ◽  
Cellular Apoptosis ◽  
Signalling Transduction ◽  
The One ◽  
New Evidence

When brain injury happens, endogenous neural stem cells (NSCs) located in the adult subventricular zone (SVZ) and subgranular zone (SGZ) are attacked by ischemia/reperfusion to undergo cellular apoptosis and death before being induced to migrate to the lesion point and differentiate into mature neural cells for damaged cell replacement. Although promoting antiapoptosis and NSC survival are critical to neuroregeneration, the mechanism has yet been elucidated clearly. Here in this study, we established an in vitro oxygen-glucose deprivation (OGD)/reoxygenation model on NSCs and detected glucose-regulated protein 78 (GRP78) involved in apoptosis, while in the absence of GRP78 by siRNA transfection, OGD/reoxygenation triggered PI3K/Akt, ERK1/2, and NF-κB/p65 activation, and induced NSC apoptosis was attenuated. Further investigation, respectively, with the inhibitor of PI3K/Akt or ERK1/2 demonstrated a blockage on GRP78 upregulation, while the inhibition of NF-κB rarely affected GRP78 induction by OGD/reoxygenation. The results indicated the bidirectional regulations of GRP78-PI3K/Akt and GRP78-ERK1/2 and the one-way signalling transduction through GRP78 to NF-κB/p65 on NSC survival from OGD/reoxygenation. In conclusion, we found that GRP78 mediated the signalling cross talk through PI3K/Akt, ERK1/2, and NF-κB/p65, which leads to antiapoptosis and NSC survival from ischemic stroke. Our finding gives a new evidence of GRP78 in NSCs as well as a new piece of signalling mechanism elucidation to NSC survival from ischemic stroke.

Upregulated long noncoding RNA Snhg1 promotes the angiogenesis of brain microvascular endothelial cells after oxygen–glucose deprivation treatment by targeting miR-199a

2018 ◽  
Vol 96 (9) ◽  
pp. 909-915 ◽  
Author(s):  
Zhengfeng Wang ◽  
Ruihua Wang ◽  
Kai Wang ◽  
Xianzhi Liu
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Brain Microvascular Endothelial Cells ◽  
Aberrant Expression ◽  
Microvascular Endothelial

Angiogenesis after ischemic stroke has important clinical significance, which stimulates endogenous recovery mechanisms and improves the neurological outcome. Enhancing angiogenesis may facilitate the function recovery from ischemic stroke. Recent studies have shown that aberrant expression of long noncoding RNAs (lncRNAs) is related to angiogenesis after ischemic stroke. Snhg1, a cancer-related lncRNA, has been reported to be upregulated after stroke. However, little is known about its role in stroke. In this study, we performed in vitro experiments to investigate the effects of Snhg1 on cell survival and angiogenesis and molecular mechanism in ischemic stroke. Oxygen–glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemia/reperfusion injury in vitro. Sngh1 was increased in brain microvascular endothelial cells (BMECs) with the prolongation of exposure to OGD, and promoted BMEC survival under OGD/R condition, and angiogenesis after OGD/R treatment. miR-199a was identified and validated to be a direct target of Snhg1, and function effects of Snhg1 on BMEC survival and angiogenesis depended on miR-199a, which is involved in the regulation of hypoxia inducible factor and vascular endothelial cell growth factor expression. These findings contribute to a better understanding of the pathogenesis of ischemic stroke and facilitate the development of proangiogenesis therapy for this disease.

scholarly journals LINGO-1 shRNA protects the brain against ischemia/reperfusion injury by inhibiting the activation of NF-κB and JAK2/STAT3

Human Cell ◽  
2021 ◽  
Author(s):  
Jiaying Zhu ◽  
Zhu Zhu ◽  
Yipin Ren ◽  
Yukang Dong ◽  
Yaqi Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Mice Model ◽  
Down Regulation

AbstractLINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, middle cerebral artery occlusion/reperfusion (MACO/R) mice model and HT22 cell oxygen–glucose deprivation/reperfusion (OGD/R) were established to simulate the pathological process of cerebral ischemia in vivo and in vitro and to detect the relevant mechanism. We found that LINGO-1 mRNA and protein were upregulated in mice and cell models. Down-regulation LINGO-1 improved the neurological symptoms and reduced pathological changes and the infarct size of the mice after MACO/R. In addition, LINGO-1 interference alleviated apoptosis and promoted cell proliferation in HT22 of OGD/R. Moreover, down-regulation of LINGO-1 proved to inhibit nuclear translocation of p-NF-κB and reduce the expression level of p-JAK2 and p-STAT3. In conclusion, our data suggest that shLINGO-1 attenuated ischemic injury by negatively regulating NF-KB and JAK2/STAT3 pathways, highlighting a novel therapeutic target for ischemic stroke.

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