scholarly journals Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

2018 ◽  
Vol 46 (5) ◽  
pp. 1793-1806 ◽  
Author(s):  
Dong-Mei Wu ◽  
Xin-Rui Han ◽  
Xin Wen ◽  
Shan Wang ◽  
Shao-Hua Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Protein Levels ◽  
Licl Treatment ◽  
Gsk 3Β

Background/Aims: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

scholarly journals Glutamine Improves Oxidative Stress through the Wnt3a/β-Catenin Signaling Pathway in Alzheimer’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yuan Wang ◽  
Qiang Wang ◽  
Jie Li ◽  
Gang Lu ◽  
Zhibin Liu
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Stress Injury ◽  
Mda Content ◽  
Samp8 Mice

Background/Aims. Alzheimer’s disease (AD) is the most common neurodegenerative disease, and all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. In this study, we hypothesized that glutamine (Gln) offers protection against oxidative stress injury in SAMP8 mice as well as the underlying mechanism. Methods. The SAMP8 mice received glutamine intragastrically for 8 consecutive weeks to evaluate the protective effect of glutamine on oxidative stress in AD mice involving Wnt3a/β-catenin signaling pathway. In addition, rat pheochromocytoma tumor cell line PC12 was pretreated with 32 μM glutamine for 2 h followed by 24 h incubation with 40 μM Aβ25-35 to obtain in vitro data. Results. In vivo the administration of glutamine was found to ameliorate behavioral deficits and neuron damage, increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-XP) activity, reduce the malondialdehyde (MDA) content, and activate the Wnt3a/β-catenin signaling pathway in SAMP8 mice. In vitro glutamine treatment decreased the toxicity of Aβ25-35 on PC12 cells and prevented apoptosis. Additionally, glutamine treatment increased SOD and GSH-XP activity and decreased MDA content and increased Wnt3a and β-catenin protein levels. Interestingly, the DKK-1 (Wnt3a/β-catenin pathway inhibitor) decreased the antioxidant capacity of glutamine in Aβ25-35-treated PC12 cells. Conclusion. This study suggests that glutamine could protect against oxidative stress-induced injury in AD mice via the Wnt3a/β-catenin signaling pathway.

scholarly journals Hyperoside Protected Against Oxidative Stress-Induced Liver Injury via the PHLPP2-AKT-GSK-3β Signaling Pathway In Vivo and In Vitro

2020 ◽  
Vol 11 ◽  
Author(s):  
Haiyan Xing ◽  
Ruoqiu Fu ◽  
Caiyi Cheng ◽  
Yongqing Cai ◽  
Xianfeng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Gsk 3Β

scholarly journals Overexpression of FBXO17 Promotes the Proliferation, Migration and Invasion of Glioma Cells Through the Akt/GSK-3β/Snail Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972110073
Author(s):  
Ning Wang ◽  
Qian Song ◽  
Hai Yu ◽  
Gang Bao
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Vimentin Expression ◽  
Protein Levels ◽  
Cellular Behaviors ◽  
Gsk 3Β

FBXO17 is a newly studied F-box protein associated with high-grade glioma. However, its exact role in glioma remains unclear. In the present study, we aimed to investigate the role of FBXO17 in glioma both in vitro and in vivo and explore the underlying mechanism. Our results showed that FBXO17 mRNA and protein levels were upregulated in glioma cells including U87, U251, SHG44, and U-118-MG cells as compared to the HA1800 cells. Downregulation of FBXO17 significantly suppressed the cellular behaviors of glioma cells including cell proliferation, migration, and invasion. In addition, FBXO17 knockdown induced E-cadherin expression and inhibited N-cadherin and vimentin expression at mRNA and protein levels in glioma cells. In contrast, overexpression of FBXO17 promoted cell proliferation, migration, invasion and EMT process. Furthermore, FBXO17 regulated the Akt/GSK-3β/snail signaling pathway in glioma cells with significant changes in the expression levels of p-Akt, p-GSK-3β and snail. Additionally, inhibition of Akt by LY294002 reversed the effects of FBXO17 overexpression on cellular behaviors of glioma cells. Finally, in vivo mouse xenograft assay proved that downregulation of FBXO17 suppresses the tumorigenesis of glioma. In conclusion, these findings demonstrated that FBXO17 acted as a promotor of glioma development via modulating Akt/GSK-3β/snail signaling pathway.

scholarly journals Mechanisms of Trx2/ASK1-Mediated Mitochondrial Injury in Pemphigus Vulgaris

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Bin Wei ◽  
Fenghe Li
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Pemphigus Vulgaris ◽  
Stress Factors ◽  
Tissue Samples ◽  
Mitochondrial Injury ◽  
Protein Levels ◽  
Thioredoxin 2

Objective. Apoptotic events mediated by mitochondrial injury play an important role on the onset of Pemphigus vulgaris (PV). The thioredoxin-2 (Trx2)/apoptosis signal-regulating kinase 1 (ASK1) signaling pathway is considered a key cascade involved on the regulation of mitochondrial injury. Hence, we have investigated the regulatory mechanism of the Trx2/ASK1 signaling in PV-induced mitochondrial injury. Methods. Serum and tissue samples were collected from clinical PV patients to detect the oxidative stress factors, cell apoptosis, and expression of members from Trx2/ASK1 signaling. HaCaT cells were cultured with the serum of PV patients and transfected with Trx2 overexpression or silencing vector. Changes in the levels of reactive oxygen species (ROS), mitochondrial membrane potential (△ψm), and apoptosis were further evaluated. A PV mouse model was established and administered with Trx2-overexpressing plasmid. The effect of ectopic Trx2 expression towards acantholysis in PV mice was observed. Results. A series of cellular and molecular effects, including (i) increased levels of oxidative stress products, (ii) destruction of epithelial cells in the skin tissues, (iii) induction of apoptosis in keratinocytes, (iv) reduction of Trx2 protein levels, and (v) enhanced phosphorylation of ASK1, were detected in PV patients. In vitro experiments confirmed that Trx2 can inhibit ASK1 phosphorylation, alleviate ROS release, decrease △ψm, and lower the apoptotic rate. Injection of Trx2-overexpressing vectors in vivo could also relieve acantholysis and blister formation in PV mice. Conclusion. The Trx2/ASK1 signaling pathway regulates the incidence of PV mediated by mitochondrial injury.

scholarly journals Downregulation of microRNA-15b-5p Targeting the Akt3-Mediated GSK-3β/β-Catenin Signaling Pathway Inhibits Cell Apoptosis in Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianzhong Zhu ◽  
Xue Xu ◽  
Yingyin Liang ◽  
Ronglan Zhu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Luciferase Reporter ◽  
In Vivo Models ◽  
Gsk 3Β

Parkinson’s disease (PD) is an incurable progressive disorder resulting from neurodegeneration, and apoptosis is considered a dominant mechanism underlying the process of neurodegeneration. MicroRNAs (miRNAs), which are small and noncoding RNAs involved in many a biological process like apoptosis and regulation of gene expressions, have been found in postmortem brain samples of patients with PD, as well as in vitro and in vivo models of PD. To explore the impact of miR-15b-5p and Akt3 on apoptosis in the progression of PD, the method of quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed, and the analysis result showed upregulated expression of miR-15b-5p and downregulated expression of Akt3 in the serum of PD patients, MPP+-induced SH-SY5Y cells, and the brain tissues of MPTP-induced mice. Meanwhile, the dual-luciferase reporter assay was used to demonstrate the regulator-target interaction between miR-15b-5p and Akt3; flow cytometry and spectrophotometry revealed that transfection of miR-15b-5p mimic and si-Akt3 increased the rate of apoptosis and caspase-3 activity, whereas transfecting the miR-15b-5p inhibitor and Akt3-overexpression plasmid repressed the rate of apoptosis and caspase-3 activity in the MPP+-induced SH-SY5Y cell model and the MPTP-induced mouse model. Additionally, analysis of western blotting (WB) assays in vivo and in vitro revealed that proapoptosis proteins (Bax, caspase-3, GSK-3β, and β-catenin) showed markedly upregulated expression in the miR-15b-5p inhibitor and si-Akt3-overexpression groups, while the expression of an antiapoptosis gene (i.e., Bcl2) was downregulated. These analysis results indicate that downregulation of miR-15b-5p by targeting the Akt3-mediated GSK-3β/β-catenin signaling pathway would repress cell apoptosis in PD in vivo and in vitro. It is expected that the research findings would help find new therapeutic targets for treatment of PD.

miR-187 modulates cardiomyocyte apoptosis and oxidative stress in myocardial infarction mice via negatively regulating DYRK2

2021 ◽  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Protective Effect ◽  
Myocardial Infarct ◽  
Annexin V ◽  
Cardiomyocyte Apoptosis ◽  
Ros Generation ◽  
Downstream Target

Myocardial infarction is a serious representation of cardiovescular disease, MicroRNAs play a role in modifying I/R injury and myocardial infarct remodeling. The present study therefore examined the potential role of miR-187 in cardiac I/R injury and its underlying mechanisms. miR-187 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with miR-187 mimic or inhibitor to confirm the function of miR-187 in H/R. DYRK2 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with DYRK2 inhibitor. A myocardium I/R mouse model was established. Circulating levels of miR-187 or DYRK2 was detected by quantitative realtime PCR and protein expression was detected by western blotting. The cell viability in all groups was determined by MTT assay and the apoptosis ratio was detected by flow cytometry after staining with Annexin V-FITC. The effect of miR-187 on cellular ROS generation was examined by DCFH-DA. The level of lipid peroxidation and SOD expression were determined by MDA and SOD assay. The findings indicated that miR-187 may be a possible regulator in the protective effect of H/R-induced cardiomyocyte apoptosis, cellular oxidative stress and leaded to DYRK2 suppression at a posttranscriptional level. Moreover, the improvement of miR-187 on H/R-induced cardiomyocyte injury contributed to the obstruction of DYRK2 expression. In addition, these results identified DYRK2 as the functional downstream target of miR-187 regulated myocardial infarction and oxidative stress.These present work provided the first insight into the function of miR-187 in successfully protect cardiomyocyte both in vivo and in vitro, and such a protective effect were mediated through the regulation of DYRK2 expression.

scholarly journals Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Protein Levels ◽  
Key Factor ◽  
Protein Sulfhydryl ◽  
Mrna And Protein Expression ◽  
The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity

2016 ◽  
Vol 48 ◽  
pp. 253-264 ◽  
Author(s):  
Pamela Soledad Bustos ◽  
Romina Deza-Ponzio ◽  
Paulina Laura Páez ◽  
Ines Albesa ◽  
José Luis Cabrera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antimicrobial Activity ◽  
Protective Effect ◽  
Blood Cells

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

2018 ◽  
Vol 132 (6) ◽  
pp. 685-699 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
Ya-Ge Jin ◽  
Ning Li ◽  
...  
Keyword(s):  
T Cell ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

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