scholarly journals Anthocyanin attenuates oxygen-glucose deprivation/reperfusion-induced apoptosis of PC12 cells via inactivation of ASK1/JNK/p38 signaling pathway

2021 ◽  
Vol 18 (10) ◽  
pp. 2037-2043
Author(s):  
Hong Zhu ◽  
Dan Ren ◽  
Lan Xiao ◽  
Ting Zhang ◽  
Ruomeng Li ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Induced Apoptosis

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.

Protective effect of hydrogen against ischemia-reperfusion induced spinal nerve cell apoptosis

2021 ◽  
Author(s):  
Yanqing Sun ◽  
Wei Shi ◽  
Bo Yuan ◽  
Zhiwei Wang ◽  
Shengyuan Zhou ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protective Effect ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Caspase 12

Abstract Background: This study aims to explore the protective effect of hydrogen against oxygen-glucose-serum deprivation/restoration (OGSD/R)-induced PC12 cell apoptosis in vitro and the possible underlying mechanism. Methods: A normal control (NC) group was set where PC12 cells were cultured normal, while a positive control (PC) group, where PC12 cells were exposed to OGSD 12h/R1h without intervention, and a hydrogen intervention (HI) group, where PC12 cells were exposed to OGSD 12h/R1h plus HI, were conducted at the same time. At OGSD 12h/R 1h, cells were DAPI stained to detect viability and changes in the expression of apoptosis-associated proteins caspase-3, caspase-12 and CHOP/GADD153, and the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4. At the same time, the effect of HI was observed. Results: The result revealed that compared with NC group, cell apoptosis was more severe and cell viability was reduced significantly in PC group, while cell apoptosis was ameliorated and cell viability was increased significantly in HI as compared with PC group. In addition, the content of caspase-3 and caspase-12 in HI group was decreased significantly as compared with that in PC group. During this process, the endoplasmic reticulum-related signaling pathway protein PERK-eIF2α-ATF4 was activated. In HI group, the expression of this protein was decreased and cell viability was increased significantly as compared with those in PC group. Conclusions: Hydrogen was able to inhibit OGSD/R-induced PC12 cell apoptosis and exert a protective effect against ischemia-repurfusion injury (IRI) to nerve cells, probably through inhibiting the endoplasmic reticulum-related signaling pathway protein.

scholarly journals Proteomic Identification of Nrf2-Mediated Phase II Enzymes Critical for Protection of Tao Hong Si Wu Decoction against Oxygen Glucose Deprivation Injury in PC12 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Hong-yi Qi ◽  
Li Li ◽  
Jie Yu ◽  
Lu Chen ◽  
Yong-liang Huang ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Phase Ii ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Phase Ii Enzymes

Chinese herbal medicine formula Tao Hong Si Wu decoction (THSWD) is traditionally used in China for cerebrovascular diseases. However, the molecular mechanisms of THSWD associated with the cerebral ischemia reperfusion injury are largely unknown. The current study applied the two-dimensional gel electrophoresis-based proteomics to investigate the different protein profiles in PC12 cells with and without the treatment of THSWD. Twenty-six proteins affected by THSWD were identified by MALDI-TOF mass spectrometry. Gene ontology analysis showed that those proteins participated in several important biological processes and exhibited diverse molecular functions. In particular, six of them were found to be phase II antioxidant enzymes, which were regulated by NF-E2-related factor-2 (Nrf2). Quantitative PCR further confirmed a dose-dependent induction of the six phase II enzymes by THSWD at the transcription level. Moreover, the individual ingredients of THSWD were discovered to synergistically contribute to the induction of phase II enzymes. Importantly, THSWD’s protection against oxygen-glucose deprivation-reperfusion (OGD-Rep) induced cell death was significantly attenuated by antioxidant response element (ARE) decoy oligonucleotides, suggesting the protection of THSWD may be likely regulated at least in part by Nrf2-mediated phase II enzymes. Thus, our data will help to elucidate the molecular mechanisms underlying the neuroprotective effect of THSWD.

scholarly journals Morphine post-conditioning-induced up-regulation of lncRNA TINCR protects cardiomyocytes from ischemia–reperfusion injury via inhibiting degradation and ubiquitination of FGF1

QJM ◽  
2020 ◽  
Vol 113 (12) ◽  
pp. 859-869
Author(s):  
M Wang ◽  
S Liu ◽  
H Wang ◽  
R Tang ◽  
Z Chen
Keyword(s):  
Cytochrome C ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
Cytochrome C Release ◽  
Mptp Opening

Abstract Background Our previous study has demonstrated that morphine post-conditioning (MpostC) protects cardiomyocytes from ischemia/reperfusion (I/R) injury partly through activating protein kinase-epsilon (PKCε) signaling pathway and subsequently inhibiting mitochondrial permeability transition pore (mPTP) opening. Aim In this study, we aim to investigate the relationship between long non-coding RNA TINCR and PKCε in cardiomyocytes under MpostC-treated I/R injury. Design The myocardial I/R rat model was established by the ligation of lower anterior descending coronary artery for 45 min followed by the reperfusion for 1 h, and MpostC was performed before the reperfusion. Method H/R and MpostC were performed in the rat cardiomyocyte cell line (H9C2), and the Cytochrome-c release in cytosol and mPTP opening were determined. Cell viability was detected by using Cell Counting Kit-8, and cell apoptosis was determined by using flow cytometry or TUNEL assay. Results The results indicated that MpostC restored the expression of TINCR in I/R rat myocardial tissues. In cardiomyocytes, the therapeutic effect of MpostC, including reduced mPTP opening, reduced Cytochrome-c expression, increased cell viability and reduced cell apoptosis, was dramatically negated by interfering TINCR. The expression of fibroblast growth factor 1 (FGF1), a protein that activates PKCε signaling pathway, was positively correlated with TINCR. The RNA immunoprecipitation and RNA pull-down assay further confirmed the binding between FGF1 and TINCR. Furthermore, TINCR was demonstrated to inhibit the degradation and ubiquitination of FGF1 in cardiomyocytes using the cycloheximide experiment and the ubiquitination assay. The TINCR/FGF1/PKCε axis was revealed to mediate the protective effect of MpostC against hypoxia/reoxygenation injury both in vitro and in vivo. Conclusion In conclusion, our findings demonstrated that MpostC-induced up-regulation of TINCR protects cardiomyocytes from I/R injury via inhibiting degradation and ubiquitination of FGF1, and subsequently activating PKCε signaling pathway, which provides a novel insight in the mechanism of TINCR and PKCε during MpostC treatment of I/R injury.

scholarly journals Ketamine and Propofol Protect Neuron Cells from Oxygen-Glucose Deprivation-Induced Injury through SAPK/JNK Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Aihua Qi ◽  
Yiyun Cao ◽  
Aizhong Wang
Keyword(s):  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
3D Culture ◽  
Annexin V ◽  
Glucose Deprivation ◽  
Signalling Pathway ◽  
Oxygen Glucose Deprivation ◽  
Neuronal Pc12 Cells ◽  
Time Point

Ketamine and propofol are commonly used anaesthetic reagents. Recent research revealed that ketamine and propofol have an important role in cell survival. However, it remains unknown whether they affect the outcome of hypoxic-ischemic brain injury. To address this issue, we in this study investigated the effects of ketamine and propofol on the survival and proliferation of neuronal PC12 cells after exposure to oxygen-glucose deprivation- (OGD-) induced injury. PC12 cells were maintained under a 3-dimensional (3D) culture system to mimic a real physiological microenvironment. The cell injury was induced by 5% CO2 and 95% N2 for a different time point. MTT assay was used for the cell proliferation assay. The cell apoptosis was evaluated by annexin V and propidium iodide (PI) labeling, immunofluorescence staining, transmission electron microscopy (TEM), flow cytometry, and Western blot, respectively. Our results showed that PC12 cell apoptosis was significantly increased for up to 70% after the cells were treated with OGD for 24 hours and reduced to baseline at the 72-hour time point. However, pretreatment with ketamine and propofol significantly protected the cells from OGD-induced cell apoptosis, as evidenced by more expression of antiapoptotic Bcl-2 and lower expression of proapoptotic cleaved caspase-3, phosphor-SAPK/JNK, and phosphor-c-Jun than those of untreated control cells. Thus, we conclude that ketamine and propofol protected PC12 cells from OGD-induced cell apoptosis, at least partially through the SAPK/JNK signalling pathway.

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

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.

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

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.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

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