scholarly journals Nrf2 Pathway Ameliorates Bladder Dysfunction in Cyclophosphamide-Induced Cystitis via Suppression of Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bin Ni ◽  
Zhengsen Chen ◽  
Le Shu ◽  
Yunpeng Shao ◽  
Yi Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bladder Dysfunction ◽  
Gene Knockout ◽  
Bladder Injury ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Nrf2 Pathway ◽  
Protein Levels ◽  
Gene Knockout Mice ◽  
Pain Sensitization

Objective. To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC). Methods. We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway. Results. After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2-/- CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2+/+ CYP mice, while there were no significant changes in the Nrf2-/- CYP mice. Conclusion. Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.

Nuclear factor erythroid 2-related factor 2 rescues the oxidative stress induced by di-N-butylphthalate in testicular Leydig cells

2014 ◽  
Vol 34 (2) ◽  
pp. 145-152 ◽  
Author(s):  
B Shen ◽  
W Wang ◽  
L Ding ◽  
Y Sao ◽  
Y Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cells ◽  
Target Genes ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes ◽  
Protein Levels

Aim: This study aimed to determine whether nuclear factor erythroid 2-related factor 2 antagonized the oxidative stress induced by di- N-butylphthalate (DBP) in testicular Leydig cells. Methods: Mouse TM3 testicular Leydig cells were treated with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP. Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and the effects of Nrf2 inducer sulphoraphane (SFN) were tested. Results: DBP induced intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and protein levels of Nrf2 were increased together with its target genes, namely heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP. Conclusion: Increased Nrf2 activity, for example, by SFN can effectively antagonize the oxidative stress in testicular Leydig cells caused by DBP.

scholarly journals N-acetylcysteine alleviates PCB52-induced hepatotoxicity by repressing oxidative stress and inflammatory responses

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9720
Author(s):  
Wen-Tao Zhou ◽  
Li-Bin Wang ◽  
Hao Yu ◽  
Kai-Kai Zhang ◽  
Li-Jian Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Inflammatory Responses ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Nrf2 Pathway ◽  
Protein Levels ◽  
Saline Pretreatment

Polychlorinated biphenyls (PCBs), particularly low chlorinated congeners in our environment, can induce human hepatotoxicity. However, the mechanisms by which PCBs cause hepatotoxicity remain elusive. Moreover, there are no effective treatments for this condition. In this study, 40 μM PCB52 was administered to rat (Brl-3A) and human hepatocytes (L-02) for 48 h following the N-acetylcysteine (NAC)/saline pretreatment. A significant decrease in cell viability was observed in PCB52-treated cells relative to the control. Besides, PCB52 significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents, suggesting induction of oxidative stress. The expression of Traf6, MyD88, and Tnf in Brl-3A cells and that of MYD88, TNF, and IL1B in L-02 cells were significantly upregulated by PCB52. Consistently, overexpression of TLR4, MyD88, Traf6, and NF-κB p65 proteins was observed in PCB52-treated cells, indicating activation of inflammatory responses. Nevertheless, no changes in kelch-like ECH-associated protein 1 (keap1), nuclear factor-erythroid 2-related factor (nrf2), and heme oxygenase-1 proteins were observed in PCB52-treated cells, indicating non-activation of the keap1/nrf2 pathway. Pretreatment with NAC significantly ameliorated PCB52 effects on cell viability, ROS levels, MDA contents and expression of inflammatory elements at both RNA and protein levels. However, no changes in keap1, nrf2 and HO-1 protein levels were detected following NAC pretreatment. Taken together, with non-activated keap1/nrf2 pathway, PCB52-induced oxidative stress and inflammatory responses could be responsible for its hepatotoxicity. These effects were effectively attenuated by NAC pretreatment, which scavenges ROS and dampens inflammatory responses. This study might provide novel strategies for the treatment of the PCBs-associated hepatotoxic effects.

scholarly journals Apigenin Protects Against Renal Tubular Epithelial Cell Injury and Oxidative Stress by High Glucose via Regulation of NF-E2-Related Factor 2 (Nrf2) Pathway

2019 ◽  
Vol 25 ◽  
pp. 5280-5288 ◽  
Author(s):  
Jichen Zhang ◽  
Xuemei Zhao ◽  
Hongling Zhu ◽  
Jingnan Wang ◽  
Junhua Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
High Glucose ◽  
Cell Injury ◽  
Tubular Epithelial Cell ◽  
Related Factor ◽  
Renal Tubular Epithelial Cell ◽  
Nrf2 Pathway ◽  
Renal Tubular ◽  
And Oxidative Stress

scholarly journals Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Rong Wang ◽  
Yongzheng Luo ◽  
Yadong Lu ◽  
Daojuan Wang ◽  
Tingyu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Experimental Colitis ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Related Factor ◽  
Protective Effects ◽  
Protein Levels ◽  
Bowel Diseases ◽  
Effective Therapeutic Strategy ◽  
And Oxidative Stress

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

scholarly journals Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases

2019 ◽  
Vol 20 (13) ◽  
pp. 3208 ◽  
Author(s):  
Fabiane Valentini Francisqueti-Ferron ◽  
Artur Junio Togneri Ferron ◽  
Jéssica Leite Garcia ◽  
Carol Cristina Vágula de Almeida Silva ◽  
Mariane Róvero Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcriptional Factor ◽  
Future Research ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Age Related ◽  
Basic Concepts

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

ARNT Mediates Chemotherapy Resistance by Modulating the Response to Oxidative Stress in AML Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2737-2737
Author(s):  
Richard A. Wells ◽  
Chunhong Gu ◽  
Joelle dela Paz
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Lines ◽  
Akt Signaling ◽  
Mrna Levels ◽  
Antioxidant Genes ◽  
Protein Levels ◽  
Exogenous Expression ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Abstract Abstract 2737 Poster Board II-713 Background Although patients with acute myelogenous leukaemia (AML) typically respond well to initial therapy, with over 75% of patients achieving complete remission, in the great majority the disease ultimately relapses. This is thought to be due to the inherent resistance of leukaemia stem cells to the effects of chemotherapy. While some mechanisms of chemoresistance, e.g. TP53 mutation and upregulation of P-glycoprotein expression, have been well characterized, this phenomenon remains incompletely understood and is a significant barrier to improving patient outcomes. Methods and results The thiazolidindione drug troglitazone (TG) induces apoptosis in AML cells via generation of intracellular reactive oxygen species (ROS), but the degree of sensitivity to TG is highly heterogeneous among AML cell lines. We studied expression of the transcription factor ARNT (aryl hydrocarbon nuclear translocator) in TG-sensitive and TG-resistant AML cell lines following TG treatment. In HL-60 cells, which are highly sensitive to induction of apoptosis by TG, ARNT mRNA levels remained constant following TG treatment and ARNT protein levels markedly decreased, while in U937 cells, which are TG resistant, ARNT mRNA levels increased and ARNT protein levels remained constant. We then tested the effect of exogenous expression of ARNT on the sensitivity of HL-60 cells to TG-induced apoptosis. HL-60 cells transduced with a retrovirus expressing ARNT became TG-resistant. Exogenous expression of ARNT also conferred resistance to induction of apoptosis by hydrogen peroxide, daunorubicin and etoposide. The cellular response to oxidative stress is governed by intracellular signaling pathways and through a transcriptional response through which expression of antioxidant genes is coordinated. HL-60 cells expressing ARNT had striking constitutive activation of AKT signaling, and treatment of these cells with a specific inhibitor of AKT signaling reversed their resistance to TG-induced apoptosis. The activation of AKT signaling by ARNT appears to be mediated by downregulation of expression of PP2A and alpha4, two key negative regulators of AKT phosphorylation. In addition, ARNT-transduced HL-60 cells showed increased expression of Nrf2, a key transcriptional regulator of the antioxidant response, and its target genes SOD2 and CAT. Conclusions The response to oxidative stress is heterogeneous in AML cells lines, and varies with expression of ARNT. ARNT activates expression of Nrf2, which stimulates expression of antioxidant genes resulting in an augmented adaptive response to ROS. Unexpectedly, ARNT also activates AKT signaling by repressing expression of the regulatory phosphatases PP2A and alpha4. These activities of ARNT result in increased resistance to the induction of apoptosis by TG, hydrogen peroxide, and chemotherapy. ARNT may play an important role in chemoresistance in and may be useful as a predictive or prognostic biomarker. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative stress status in patients with silicosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yingzheng Zhao ◽  
Guangcui Xu ◽  
Haibin Li ◽  
Meiyu Chang ◽  
Cheng Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress State ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Related Factor ◽  
Healthy Controls ◽  
Rna Seq ◽  
Antioxidant Genes

Abstract Background The immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative stress state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified. Methods Ninety-two male patients with silicosis and 87 male healthy volunteers were randomly selected. PBMCs were isolated from fresh blood from patients with silicosis and healthy controls. The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls. Results The number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7. Conclusions These findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.

scholarly journals Sodium arsenite induces spatial learning and memory impairment associated with oxidative stress and activates the Nrf2/PPARγ pathway against oxidative injury in mice hippocampus

2021 ◽  
Author(s):  
Liang Xiong ◽  
Jinyu Huang ◽  
Ying Gao ◽  
Yanfang Gao ◽  
Chunmei Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sodium Arsenite ◽  
Defense Mechanism ◽  
Antioxidant Defenses ◽  
Spatial Learning And Memory ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Pparγ Expression

Abstract Arsenic (As) is a ubiquitous environmental and industrial toxin with known correlates of oxidative stress and cognitive deficits in the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that represents a central cellular antioxidant defense mechanism and transcribes many antioxidant genes. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a well-known nuclear receptor to regulate lipid metabolism in many tissues, and it has been also associated with the control of oxidative stress, neuronal death, neurogenesis and differentiation. The role of Nrf2 and PPARγ in As-induced neurotoxicity is still debated. The present study was designed to investigate the neurobehavioral toxic effect of sub-chronic and middle-dose sodium arsenite exposure in mice hippocampus, as well as the response of Nrf2/PPARγ expression and influence on protein expression levels of their downstream antioxidant genes. Our results showed that mice treated with intraperitoneal injection of sodium arsenite (50 mg/kg body wt.) twice a week for 7 weeks resulted in increased generation of reactive oxygen species and impairment of spatial cognitive function. The present study also found a positive association between Nrf2/PPARγ expression in hippocampus of mice, and activation of antioxidant defenses by the evidently upregulated expression of their downstream genes, including superoxide dismutase, heme oxygenase-1 and glutathione peroxidase-3. Therefore, our findings were helpful for further understanding the role of Nrf2/PPARγ feedback loop in As-induced neurobehavioral toxicity.

scholarly journals Cytoprotective Effect of Ligustrum robustum Polyphenol Extract against Hydrogen Peroxide-Induced Oxidative Stress via Nrf2 Signaling Pathway in Caco-2 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jiayi Chen ◽  
Fangting He ◽  
Sijing Liu ◽  
Tao Zhou ◽  
Saira Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Signaling Pathway ◽  
Total Phenolic ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cytoprotective Effect ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes ◽  
Nrf2 Signaling Pathway

Ligustrum robustum is a traditional herbal tea that is widely distributed in southwest China. The health effects of L. robustum are characteristics of clearing heat, antioxidant, inducing resurgence, and improving digestion. However, the molecular mechanisms related to these effects, particularly the antioxidant mechanism, have been seldom reported. The objective of this study was to assess antioxidative capacity of L. robustum, and its protective effects and mechanisms against hydrogen peroxide (H2O2) - induced toxicity in Caco-2 cells. Total phenolic contents, free radical scavenging activity, and reducing capacity of L. robustum were measured. The effects of L. robustum on the cell viability and antioxidant defense system were explored. The expression of nuclear factor E2 related factor 2 (Nrf2) and antioxidant genes: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate cysteine ligase (GCL) were analyzed by western blot and qPCR. Pretreatment of L. robustum could significantly reduce H2O2-induced toxicity, decrease the level of reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR). By activating the expression of Nrf2 and antioxidant genes (NQO1, HO-1, and GCL), L. robustum exerts cytoprotective effect in Caco-2 cells dealt with H2O2. Therefore, the well-established model of Caco-2 cells demonstrates that L. robustum may modulate the cytoprotective effect against the H2O2-induced oxidative stress through the Nrf2 signaling pathway.

scholarly journals Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice

2019 ◽  
Vol 317 (4) ◽  
pp. F906-F912
Author(s):  
Rania A. Elrashidy ◽  
Michael Kavran ◽  
Mervat E. Asker ◽  
Hoda E. Mohamed ◽  
Firouz Daneshgari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Bladder Dysfunction ◽  
Gene Knockout ◽  
Immunoblot Analysis ◽  
Bladder Function ◽  
Detrusor Muscle ◽  
Diabetic Mice ◽  
Wild Type ◽  
Apoptotic Pathways

Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We tested the hypothesis that oxidative stress plays a key role in the development of diabetic bladder dysfunction using an inducible smooth muscle (SM)-specific superoxide dismutase 2 ( Sod2) gene knockout (SM- Sod2 KO) mouse model. Eight-week-old male Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice and wild-type mice were assigned to diabetic or control groups. 4-Hydroxytamoxifen was injected into Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice to activate CreERT2-mediated deletion of Sod2. Diabetes was induced by injection of streptozotocin, whereas control mice were injected with vehicle. Nine weeks later, bladder function was evaluated, and bladders were harvested for immunoblot analysis. Wild-type diabetic mice presented compensated bladder function along with increased nitrotyrosine and MnSOD in detrusor muscle. Induction of diabetes in SM- Sod2 KO mice caused deteriorated bladder function and even greater increases in nitrotyrosine compared with wild-type diabetic mice. Expression levels of apoptosis regulator Bax and cleaved caspase-3 were increased, but apoptosis regulator Bcl-2 expression was decreased in detrusor muscle of both diabetic groups, with more pronounced effects in SM- Sod2 KO diabetic mice. Our findings demonstrate that exaggerated oxidative stress can accelerate the development of bladder dysfunction in diabetic mice and the enhanced activation of apoptotic pathways in the bladder may be involved in the process.

Sign in / Sign up

Export Citation Format

Share Document