scholarly journals Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal

2012 ◽  
Vol 2 (1) ◽  
pp. 40 ◽  
Author(s):  
Ying Huang ◽  
Wenge Li ◽  
Ah-Ng Kong
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Related Factor ◽  
Detoxifying Enzymes

Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice

2010 ◽  
Vol 298 (2) ◽  
pp. G283-G294 ◽  
Author(s):  
Hirokazu Sugimoto ◽  
Kosuke Okada ◽  
Junichi Shoda ◽  
Eiji Warabi ◽  
Kazunori Ishige ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rapid Onset ◽  
Related Factor ◽  
Pathological State ◽  
Mrna Levels ◽  
Detoxifying Enzymes ◽  
Stress Genes ◽  
Promising Target ◽  
Antioxidative Stress ◽  
Transcriptional Pathway

Oxidative stress is a critical mediator in liver injury of steatohepatitis. The transcription factor Nrf2 serves as a cellular stress sensor and is a key regulator for induction of hepatic detoxification and antioxidative stress systems. The involvement of Nrf2 in defense against the development of steatohepatitis remains unknown. We aimed to investigate the protective roles of Nrf2 in nutritional steatohepatitis using wild-type (WT) and Nrf2 gene-null ( Nrf2-null) mice. WT and Nrf2-null mice were fed a methionine- and choline-deficient (MCD) diet for 3 and 6 wk, and the liver tissues were analyzed for pathology and for expression levels of detoxifying enzymes and antioxidative stress genes via the Nrf2 transcriptional pathway. In WT mice fed an MCD diet, Nrf2 was potently activated in the livers, and steatohepatitis did not develop over the observation periods. However, in Nrf2-null mice fed an MCD diet, the pathological state of the steatohepatitis was aggravated in terms of fatty changes, inflammation, fibrosis, and iron accumulation. In the livers of the Nrf2-null mice, oxidative stress was significantly increased compared with that of WT mice based on the increased levels of 4-hydroxy-2-nonenal and malondialdehyde. This change was associated with the decreased levels of glutathione, detoxifying enzymes, catalase, and superoxide dismutase activity. Correlating well with the liver pathology, the mRNA levels of factors involved in fatty acid metabolism, inflammatory cytokines, and fibrogenesis-related genes were significantly increased in the livers of the Nrf2-null mice. These findings demonstrate that Nrf2 deletion in mice leads to rapid onset and progression of nutritional steatohepatitis induced by an MCD diet. Activation of Nrf2 could be a promising target toward developing new options for prevention and treatment of steatohepatitis.

scholarly journals SLC7A11 Reduces Laser-Induced Choroidal Neovascularization by Inhibiting RPE Ferroptosis and VEGF Production

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Min Gao ◽  
Jian Liang ◽  
Yuhong Chen ◽  
Yimin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Viability ◽  
Laser Treatment ◽  
Choroidal Neovascularization ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Rpe Cells ◽  
Age Related

In age-related macular degeneration (AMD), one of the principal sources of vascular endothelial growth factor (VEGF) is retinal pigment epithelium (RPE) cells under hypoxia or oxidative stress. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate transporter, regulates the level of cellular lipid peroxidation, and restrains ferroptosis. In our study, we assessed the role of SLC7A11 in laser-induced choroidal neovascularization (CNV) and explored the underlying mechanism. We established a mouse model of CNV to detect the expression level of SLC7A11 and VEGF during disease progression. We found the expression of the SLC7A11 protein in RPE cells peaked at 3 days after laser treatment, which was correlated with the expression of VEGF. Intraperitoneal injection of SLC7A11 inhibitor expanded the area of CNV. We examined functional proteins related to oxidative stress and Fe2+ and found laser-induced ferroptosis accompanied by increased Fe2+ content and GPX4 expression in the RPE-choroidal complex after laser treatment. We verified the expression of SLC7A11 in the ARPE19 cell line and the effects of its inhibitors on cell viability and lipid peroxidation in vitro. Application of SLC7A11 inhibitor and SLC7A11 knockdown increased the level of lipid peroxidation and reduced the cell viability of ARPE19 which can be rescued by ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1). Conversely, SLC7A11 overexpression induced resistance to erastin or RSL3-induced ferroptosis. Moreover, we tested the possible regulatory transcription factor NF-E2-related factor 2 (NRF2) of SLC7A11 by Western blot. Knock-down of NRF2 decreased the expression of SLC7A11. Our study suggests that SLC7A11 plays a key role in the laser-induced CNV model by protecting RPE cells from ferroptosis. SLC7A11 provides a new therapeutic target for neovascular AMD patients.

scholarly journals Caveolae, CAVIN1, and lipid peroxidation mediate the oxidative stress response

2021 ◽  
Author(s):  
Yeping Wu ◽  
Ye-Wheen Lim ◽  
David A Stroud ◽  
Nick Martel ◽  
Thomas E. Hall ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Quantitative Proteomics ◽  
Cellular Response ◽  
Direct Interaction ◽  
Related Factor ◽  
The Novel ◽  
Biological Functions ◽  
Structural Protein ◽  
Mechanistic Studies

Caveolae have been linked to a number of biological functions but their precise roles are as yet unclear. Here we have undertaken an unbiased approach to characterize the cellular proteome regulated by the caveolar structural protein, CAVIN1, by utilizing genome-edited cells together with whole cell quantitative proteomics. Pathway analysis identified the cellular response to oxidative stress as the most significant effect of CAVIN1 loss. Functional experiments showed that sensitivity to oxidative stress was compromised in CAVIN1-null cells and zebrafish knockout lines. Mechanistic studies identified oxidative stress-triggered lipid peroxidation as the novel upstream mechanism for caveolar disassembly and release of CAVIN1. Disassembly of caveolae allows direct interaction of CAVIN1 and nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant activator. This causes NRF2 sequestration and degradation in the cytosol, inhibiting its transcriptional function in the nucleus. Thus caveolae, via lipid peroxidation and CAVIN1 release, regulate cellular susceptibility to oxidative stress-induced ferroptosis.

scholarly journals Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1

2020 ◽  
Vol 21 (10) ◽  
pp. 3716 ◽  
Author(s):  
Josué Rivera-Pérez ◽  
Martín Martínez-Rosas ◽  
César A. Conde-Castañón ◽  
Julia D. Toscano-Garibay ◽  
Nancy J. Ruiz-Pérez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protective Effect ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion ◽  
Neuronal Cells ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna Levels ◽  
Neuroprotective Efficacy

Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0–30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression.

Determination of NRF2 and GSTM1 Expression and Biomarkers of Oxidative Stress on Smoking and Nonsmoking Sperm: A Pilot study

2020 ◽  
Author(s):  
Nasim Bidram ◽  
Amir Nili-Ahmadabadi ◽  
Iraj Javadi ◽  
Seyedmahdi Tabatabaei
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lipid Peroxidation ◽  
Semen Quality ◽  
Sperm Quality ◽  
Sperm Concentration ◽  
Quality Parameters ◽  
Semen Parameters ◽  
Related Factor ◽  
Biomarkers Of Oxidative Stress

Background and Aims: Smoking has an influence on different semen parameters. It is regarded as a risk factor for infertility. This study aims to evaluate the effect of smoking cigarettes on the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione S-transferase Mu 1 (GSTM1) genes and biomarkers of oxidative stress in sperm. Materials and Methods: A case-control study was conducted on 15 men smoker (case) and 15 men nonsmokers (control) who had referred to infertility clinics in Isfahan, Iran. After sampling and analysis of semen quality parameters, gene expression of NRF2 and GSTM1 was determined using a Real time-polymerase chain reaction instrument. The lipid peroxidation and total antioxidant capacity (TAC) were evaluated by colorimetric methods. Results: Sperm concentration and their progressive motility in smokers were significantly lower than the nonsmoker population (p<0.001). In addition, the lipid peroxidation level increased and TAC level (p<0.01) as well as gene expression of NRF2 (p<0.05) and GSTM1 (p<0.01) decreased compared to control groups. Conclusions: Our data demonstrated that the NRF2 and GSMT1 expressions are significantly lower in human males with low sperm motility and correlated with specific sperm quality parameters.

scholarly journals 2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 465 ◽  
Author(s):  
Tien-Yuan Wu ◽  
Jia-Ni Lin ◽  
Zi-Yao Luo ◽  
Chuan-Jen Hsu ◽  
Jen-Shu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Morphological Changes ◽  
Critical Role ◽  
Free Radical Scavenger ◽  
Ros Generation ◽  
Radical Scavenger ◽  
Protective Mechanism ◽  
Related Factor ◽  
Detoxifying Enzymes

Oxidative stress plays a critical role in the pathogenesis of hearing loss, and 2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) exerts antioxidant effects by inhibiting reactive oxygen species (ROS) generation. With the aim of developing new therapeutic strategies for oxidative stress, this study investigated the protective mechanism of THSG in vitro using a normal mouse cochlear cell line (UB/OC-2). The THSG and ascorbic acid have similar free radical scavenger capacities. H2O2, but not THSG, reduced the UB/OC-2 cell viability. Moreover, H2O2 might induce apoptosis and autophagy by inducing morphological changes, as visualized by microscopy. As evidenced by Western blot analysis and monodansylcadaverine (MDC) staining, THSG might decrease H2O2-induced autophagy. According to a Western blotting analysis and Annexin V/PI and JC-1 staining, THSG might protect cells from H2O2-induced apoptosis and stabilize the mitochondrial membrane potential. Furthermore, THSG enhanced the translocation of nucleus factor erythroid 2-related factor 2 (Nrf2) into the nucleus and increased the mRNA and protein expression of antioxidant/detoxifying enzymes under H2O2-induced oxidative stress conditions. Collectively, our findings demonstrate that THSG, as a scavenging agent, can directly attenuate free radicals and upregulate antioxidant/detoxifying enzymes to protect against oxidative damage and show that THSG protects UB/OC-2 cells from H2O2-induced autophagy and apoptosis in vitro.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

Resistance of erythrocytes from Brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome

2011 ◽  
Vol 14 (3) ◽  
pp. 443-448 ◽  
Author(s):  
N. Kurhalyuk ◽  
H. Tkachenko ◽  
K. Pałczyńska
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Brown Trout ◽  
Salmo Trutta ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Thiobarbituric Acid Reactive Substance ◽  
Tbars Level ◽  
Reactive Substance ◽  
Brown Trout Salmo Trutta

Resistance of erythrocytes from Brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome In the present work we evaluated the effect of ulcerative dermal necrosis (UDN) syndrome on resistance of erythrocytes to haemolytic agents and lipid peroxidation level in the blood from brown trout (Salmo trutta m. trutta L.). Results showed that lipid peroxidation increased in erythrocytes, as evidenced by high thiobarbituric acid reactive substance (TBARS) levels. Compared to control group, the resistance of erythrocytes to haemolytic agents was significantly lower in UDN-positive fish. Besides, UDN increased the percent of hemolysated erythrocytes subjected to the hydrochloric acid, urea and hydrogen peroxide. Results showed that UDN led to an oxidative stress in erythrocytes able to induce enhanced lipid peroxidation level, as suggested by TBARS level and decrease of erythrocytes resistance to haemolytic agents.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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