scholarly journals Astragaloside IV ameliorates high glucose‑induced HK‑2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway

2019 ◽  
Author(s):  
Jing Wang ◽  
Hong‑Min Guo
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Astragaloside Iv ◽  
And Oxidative Stress

Downregulation of General Control Nonderepressible 2/Eukaryotic Initiation Factor 2α Attenuates Inflammation, Oxidative Stress and Cell Apoptosis in Retinal Cells Induced by High Glucose

2021 ◽  
Vol 11 (8) ◽  
pp. 1497-1505
Author(s):  
Shuyu Zhao ◽  
Yuqian Yin ◽  
Hong Qin
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Western Blot ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Colorimetric Method ◽  
Underlying Mechanism ◽  
Initiation Factor ◽  
Western Blot Assay ◽  
And Oxidative Stress

Background: Diabetic retinopathy (DR), the frequent complication of diabetes mellitus, has been the main factor of clinical blindness. It is of great clinical significance to seek a novel therapeutic target of DR. The present study aims to investigate the important role of GCN2/eIF2α in DR and the underlying mechanism. Materials and Methods: The expression levels of GCN2 and p-eIF2α were measured by western blot assay and q-PCR. The inflammation levels were assessed by ELISA assay and oxidative stress was measured by colorimetric method. Then, the key proteins related to the function of endothelial cell were measured by western blot assay. Cell apoptotic rate was detected by flow cytometry and proteins related to cell apoptosis were detected by western blot assay. Results: High glucose activated GCN2/eIF2α signaling pathway in HRCECs. Downregulation of GCN2 attenuated HG-induced cell apoptosis, inflammatory and oxidative stress in HRCECs. Meanwhile, downregulation of GCN2 ameliorated HG-induced endothelial cell dysfunction. Inhibition of GCN2 inhibited p-eIF2α, ATF4, CHOP and activated UCP2. Conclusion: The results in this study proved that knockdown of GCN2 could significantly mitigate HG-induced injury, suggesting GCN2/eIF2α as a potential target for DR therapy.

Sequoyitol Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Retina Epithelial Cells

2021 ◽  
Vol 11 (5) ◽  
pp. 1003-1009
Author(s):  
Liping Hu ◽  
Rui Zhang ◽  
Jianhua Wu ◽  
Chao Feng ◽  
Li Kong
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Therapeutic Potential ◽  
Promoting Effect ◽  
Related Factors ◽  
And Oxidative Stress

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, contributing to visual impairment and blindness. Sequoyitol (Seq), a form of inositol derivatives, has been demonstrated to be a therapeutic potential for diabetes and diabetic nephropathy. The aim of this study is to explore the effects of Seq on DR. ARPE-19 cells were cultured in high glucose (HG) condition to simulate DR in vitro. Seq (1,10 and 20 µM) was applied for treatment. CCK-8 assay was performed to detect cell viability. Flow cytometry analysis was conducted to determine cell apoptosis rate. The production level of inflammatory cytokines and oxidative stress-related factors were determined using their commercial kits. The protein expressions of corresponding genes were detected using western blotting. The results revealed that Seq significantly increased cell viability and protein expression of PCNA and Ki67 which were decreased after HG induction. HG promoted cell apoptosis by decreasing protein expression of Bcl-2 and increasing protein expression of Bax and cleaved caspase-3, which was then reversed by Seq treatment. Besides, Seq abolished the promoting effects of HG on the production of pro-inflammatory cytokines and oxidative stress-related factors. Furthermore, Seq suppressed the promoting effect of HG on the activation of NF-κB signaling by inhibiting phosphorylation of kBa and NF-κB nucleus translocation. These results indicated that Seq might protect ARPE-19 cells against HG-induced cell viability, apoptosis, inflammation and oxidative stress by regulating NF-κB signaling, providing evidence for the potential application of Seq in the therapy of DR.

scholarly journals Intermittent High Glucose Enhances Apoptosis in INS-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Xiao-li Shi ◽  
Yue-zhong Ren ◽  
Jing Wu
Keyword(s):  
Oxidative Stress ◽  
Beta Cells ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Oxidative Stress Markers ◽  
Intracellular Level ◽  
High Concentration ◽  
Stress Markers ◽  
Intermittent High Glucose ◽  
And Oxidative Stress

To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducingβ-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5 mmol/L), SHG (33.3 mmol/L), and IHG (5.5 mmol/L and 33.3 mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious toβ-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.

scholarly journals Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

2021 ◽  
Vol 15 ◽  
Author(s):  
Cong Wang ◽  
Hao Chen ◽  
Hui-hui Jiang ◽  
Bin-bin Mao ◽  
Hao Yu
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mtor Pathway ◽  
Network Pharmacology ◽  
Total Flavonoids ◽  
Western Blots ◽  
And Oxidative Stress

Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

MicroRNA-124 Prevents H2O2-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 213-222 ◽  
Author(s):  
Xiu-li Gu
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Ros Production ◽  
Human Lens Epithelial Cells ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Aim: To investigate the regulation of microRNA-124 ­(miRNA-124) on NF-κB pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). Methods: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC ­viability. HLECs were divided into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H2O2, and inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. Results: The H2O2-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H2O2-induced hLEC. Conclusion: MiRNA-124 prevents H2O2-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.

scholarly journals S-ketamine alleviates carbon tetrachloride-induced hepatic injury and oxidative stress by targeting the Nrf2/HO-1 signaling pathway

2021 ◽  
Author(s):  
Weimin Xu ◽  
Peng Wang ◽  
Dalong Wang ◽  
Ke Liu ◽  
Shuaishuai Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Biochemical Parameters ◽  
Antioxidant Response ◽  
Histopathological Analysis ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
And Oxidative Stress

The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4)-induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (ALT, AST, ALP, TB and γ-GT) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (MDA, SOD, GSH, and GSH-PX). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the Nrf2/HO-1 signaling pathway were detected by western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-KET also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via up-regulation the Nrf2/HO-1 signaling pathway.

scholarly journals Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways

2021 ◽  
pp. jim-2020-001437
Author(s):  
Ming Chen ◽  
Minghui Li ◽  
Na Zhang ◽  
Wenwen Sun ◽  
Hui Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Reverse Transcription Pcr ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Interfering Rna ◽  
And Oxidative Stress

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

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