Abstract 175: Activation of Nrf2 by Exercise Training and Curcumin Contributes to Sympatho-Inhibition in Heart Failure

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Karla K Haack ◽  
Amanda M Harlow ◽  
Hanjun Wang ◽  
Irving H Zucker
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Exercise Training ◽  
Western Blot ◽  
Related Factor ◽  
Nuclear Factor ◽  
Sympathetic Outflow ◽  
Post Surgery ◽  
Nrf2 Activation ◽  
And Oxidative Stress

Chronic Heart Failure (CHF) is a disease characterized by increased Angiotensin II type 1 receptor (AT1R) signaling, sympathetic outflow, and oxidative stress. In conditions of high oxidant stress, Nuclear factor erythroid 2 related factor 2 (Nrf2) is dissociated from Kelch-like ECH associated protein 1 (Keap1) to activate antioxidant response element (ARE)genes. Nuclear factor kappa B (NF-kB) is a transcription factor downstream of AT1R that inhibits ARE transcription . Exercise training (ExT) decreases sympathetic outflow and oxidative stress, but the mechanism(s) by which ExT is protective remain unclear. The aim of this study was to investigate if ExT indirectly activates Nrf2 and if direct Nrf2 activation by curcumin (Cur) in rats with CHF would decrease sympatho-excitation and normalize AT1R pathway overactivation. Rats were ExT for 4 weeks post-surgery on a treadmill at a final speed of 25 m/min for 60 minutes, 5 days a week for 6 weeks. Western blot analyses of RVLM micropunches are summarized in the Table. Briefly, in CHF, there was a significant upregulation in NF-kB and Keap1 and a decrease in Nrf2 protein compared to sham. ExT significantly increased Nrf2 expression compared to both sham and CHF groups but normalized NF-kB and AT1R expression in CHF animals. Oral Cur (200mg/kg/day) decreased resting HR, urinary norepinephrine excretion, and renal sympathetic nerve activity in CHF animals. Western blot analyses indicated that Cur increased Nrf2, decreased NF-kB and normalized AT1R expression in the RVLM (Table). Taken together, Nrf2 activation may be protective in normalizing AT1R expression in CHF and one of the mechanisms by which ExT exerts its beneficial effects.

scholarly journals Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Juliana F. Saldanha ◽  
Viviane de O. Leal ◽  
Peter Stenvinkel ◽  
José Carlos Carraro-Eduardo ◽  
Denise Mafra
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Related Factor ◽  
Nuclear Factor ◽  
Family Protein ◽  
Nrf2 Activation ◽  
And Oxidative Stress

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promotetranscription factor nuclear factor-erythroid 2-related factor 2(Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

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.

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.

scholarly journals NRF2 as a regulator of cell metabolism and inflammation in cancer

2020 ◽  
Vol 41 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Feng He ◽  
Laura Antonucci ◽  
Michael Karin
Keyword(s):  
Oxidative Stress ◽  
Cancer Risk ◽  
Poor Prognosis ◽  
Cell Metabolism ◽  
Transcriptional Regulator ◽  
Negative Control ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor-promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer-supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1259
Author(s):  
Gyeoung Jin Kang ◽  
Eun Ji Kim ◽  
Chang Hoon Lee
Keyword(s):  
Oxidative Stress ◽  
Cardiac Fibrosis ◽  
Lipid Mediators ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nuclear Factor ◽  
Docosahexanoic Acid ◽  
Nrf2 Activation ◽  
The World ◽  
Polyunsaturated Lipids

Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation.

scholarly journals Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling

2021 ◽  
Vol 15 ◽  
Author(s):  
Yue Fu ◽  
Jianping Jia
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
No Production ◽  
Related Factor ◽  
Nuclear Factor ◽  
Qrt Pcr ◽  
Bv2 Cells ◽  
And Oxidative Stress

BackgroundNeuroinflammation and oxidative stress are two major pathological characteristics of Alzheimer’s disease (AD). Amyloid-β oligomers (AβO), a toxic form of Aβ, promote the neuroinflammation and oxidative stress in the development of AD. Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on inflammatory response and oxidative stress.ObjectivesThe main purpose of this study is to assess the influence of ISL on inflammatory response and oxidative stress in BV2 cells stimulated with AβO, and to explore the underlying molecular mechanisms.Methods3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H- tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) cytotoxicity assays were used to assess the toxic or protective effects of ISL. The expression levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays. Morphological changes in BV2 cells were assessed by immunofluorescence method. Nitric oxide (NO) assay kit was used to determinate the NO production. Western blot, qRT-PCR and immunofluorescence were used to explore the underlying molecular mechanisms.ResultsISL treatment reduced the production of inflammatory cytokines and NO, and alleviated the morphological changes in BV2 cells induced by AβO. ISL treatment further protected N2a cells from the toxic medium of AβO-stimulated BV2 cells. ISL activated nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and suppressed nuclear factor-κB (NF-κB) signaling in BV2 cells.ConclusionISL suppresses AβO-induced inflammation and oxidative stress in BV2 cells via the regulation of Nrf2/NF-κB signaling. Therefore, ISL indirectly protects neurons from the damage of toxic conditioned media.

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