Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell injury and mitochondrial dysfunction via Nrf2/SIRT3 signaling pathway

Purpose: To investigate whether the cytoprotective effect of anthocyanin (Anc) on oxygen-glucose deprivation/reperfusion (OGD/R)-induced cell injury is related to apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Methods: PC12 cells were pre-treated with various concentrations of Anc (10, 50, and 100 μg/mL) in OGD/R-induced cell injury model. The 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay was used to assess cell viability. Cell apoptosis was measured by lactic acid dehydrogenase (LDH) release assay and flow cytometry. Western blot was employed to determine the protein expressions of BCL-2, BAX, caspase-3, p-ASK1 (Thr845), p-JNK, and p-p38. Results: The results indicate that Anc increased the viability of PC12 cells after OGD/R exposure (p < 0.05), and also efficiently rescued OGD/R-induced apoptosis (p < 0.05). Mechanistic studies showed that these protective roles of Anc are related to the inhibition of ASK1/JNK/p38 signaling pathway. Conclusion: The results indicate Anc protects against OGD/R-induced cell injury by enhancing cell viability and inhibiting cell apoptosis. The underlying mechanism of action is partly via inactivation of ASK1/JNK/p38 signaling pathway. Thus, Anc has promise as a potential natural agent to prevent and treat cerebral ischemia-reperfusion injury.

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Icariside II, a PDE5 Inhibitor, Suppresses Oxygen-Glucose Deprivation/Reperfusion-Induced Primary Hippocampal Neuronal Death Through Activating the PKG/CREB/BDNF/TrkB Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.00523 ◽

2020 ◽

Vol 11 ◽

Author(s):

Fan Xu ◽

Chun Lv ◽

Yan Deng ◽

Yuangui Liu ◽

Qihai Gong ◽

...

Keyword(s):

Signaling Pathway ◽

Neuronal Death ◽

Pde5 Inhibitor ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Icariside Ii

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PTPN21 protects PC12 cell against oxygen-glucose deprivation by activating cdk5 through ERK1/2 signaling pathway

European Journal of Pharmacology ◽

10.1016/j.ejphar.2017.08.021 ◽

2017 ◽

Vol 814 ◽

pp. 226-231 ◽

Cited By ~ 6

Author(s):

Ningning Cui ◽

Hui Lu ◽

Meng Li ◽

Qiuyue Yan

Keyword(s):

Signaling Pathway ◽

Pc12 Cell ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation

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Melatonin Protects Cardiomyocytes from Oxygen Glucose Deprivation And Reperfusion-Induced Injury by Inhibiting Rac1/JNK/Foxo3a/Bim Signaling Pathway

10.21203/rs.3.rs-163573/v1 ◽

2021 ◽

Author(s):

Yulin Wang ◽

Ying Jian ◽

Xiaofu Zhang ◽

Bin Ni ◽

Mingwei Wang ◽

...

Keyword(s):

Protective Effect ◽

Signaling Pathway ◽

Cell Injury ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

H9c2 Cell ◽

Protective Mechanism ◽

H9c2 Cells

Abstract Melatonin has been shown to exert protective effect during myocardial ischemia/reperfusion (I/R). However, the underlying mechanism is not completely understood. Using the oxygen-glucose deprivation and reperfusion (OGD/R) model of H9c2 cells in vitro, we found that melatonin alleviated OGD/R-induced H9c2 cell injury via inhibiting Foxo3a/Bim signaling pathway. Inhibition of Rac1 activation contributed to the protective effect of melatonin against OGD/R injury in H9c2 cells. Additionally, melatonin inhibited OGD/R-activated Foxo3a/Bim signaling pathway through inactivation of Rac1. Furthermore, JNK inactivation was responsible for Rac1 inhibition-mediated inactivation of Foxo3a/Bim signaling pathway and decreased cell injury in melatonin-treated H9c2 cells. Taken together, these findings identified a Rac1/JNK/Foxo3a/Bim signaling pathway in melatonin-induced protective effect against OGD/R injury in H9c2 cells. This study provided a novel insight into the protective mechanism of melatonin against myocardial I/R injury.

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Microglial and neuronal cell pyroptosis induced by oxygen-glucose deprivation/reoxygenation aggravates cell injury via activation of the caspase-1/GSDMD signaling pathway

10.21203/rs.2.24263/v1 ◽

2020 ◽

Author(s):

Zhaofei Dong ◽

Qingxia Peng ◽

Kuang Pan ◽

Weijye Lin ◽

Yidong Wang

Keyword(s):

Signaling Pathway ◽

Cell Injury ◽

Ischemia Reperfusion ◽

Neuronal Cell ◽

Glucose Deprivation ◽

Enzyme Linked Immunosorbent Assay ◽

Oxygen Glucose Deprivation ◽

Ht22 Cells ◽

Caspase 1 ◽

Bv2 Cells

Abstract Background Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cells are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosis in the simulated I/R environment in vitro. Methods The BV2 and HT22 cells were treated by oxygen-glucose deprivation/reoxygenation (OGD/R). The pyroptotic cells were detected by dye uptake method. The expression levels of pyroptotic-related proteins were determined by western blotting, immunofluorescence and enzyme linked immunosorbent assay. The cell viability was assessed using MTT assay Kit. AC-YVAD-CMK, necrosulfonamide and the siRNA of Gasdermin D (GSDMD) were used to observe the inhibited effect on caspase-1 and GSDMD, respectively. A transwell co-culture model was applied to observe pyroptosis and interactions between BV2 and HT22 cell after OGD/R. Results Both BV2 and HT22 cells underwent pyroptosis after OGD/R, and the pyroptosis occurred at earlier time point in HT22 than that of BV2. Caspase-11 and Gasdermin E (GSDME) expression in BV2 and HT22 cells did not change significantly after OGD/R. Inhibition of caspase-1 or GSDMD activity, or down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells after OGD/R. Transwell studies further showed that OGD/R-treated HT22 or BV2 cells aggravated pyroptosis of adjacent non-OGD/R-treated cells, which could be relieved by inhibition of caspase-1 or GSDMD. Conclusions OGD/R induces pyroptosis of microglia and neuronal cells and aggravates cell injury via activation of caspase-1/GSDMD signaling pathway. Our findings suggest that caspase-1 and GSDMD may be therapeutic targets after cerebral I/R. Necrosulfonamide, a chemical inhibitor of GSDMD, may be a potential drug to prevent cerebral I/R-induced brain injury.

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