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https://www.readbyqxmd.com/read/28820283/n-3-pufas-induce-inflammatory-tolerance-by-formation-of-keap1-containing-sqstm1-p62-bodies-and-activation-of-nfe2l2
#1
Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Damås, Babak Razani, Trude Helen Flo, Geir Bjørkøy
Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#2
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28801166/nuclear-factor-erythroid-derived-2-like-2-nrf2-drug-discovery-biochemical-toolbox-to-develop-nrf2-activators-by-reversible-binding-of-kelch-like-ech-associated-protein-1-keap1
#3
REVIEW
Alberto Bresciani, Antonino Missineo, Mariana Gallo, Mauro Cerretani, Paola Fezzardi, Licia Tomei, Daniel Oscar Cicero, Sergio Altamura, Alessia Santoprete, Raffaele Ingenito, Elisabetta Bianchi, Robert Pacifici, Celia Dominguez, Ignacio Munoz-Sanjuan, Steven Harper, Leticia Toledo-Sherman, Larry C Park
Mechanisms that activate innate antioxidant responses, as a way to mitigate oxidative stress at the site of action, hold much therapeutic potential in diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease, where the use of antioxidants as monotherapy has not yielded positive results. The nuclear factor NRF2 is a transcription factor whose activity upregulates the expression of cell detoxifying enzymes in response to oxidative stress. NRF2 levels are modulated by KEAP1, a sensor of oxidative stress...
August 8, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28790194/characterization-of-the-potent-selective-nrf2-activator-pstc-in-cellular-and-in-vivo-models-of-pulmonary-oxidative-stress
#4
John G Yonchuk, Joseph P Foley, Brian J Bolognese, Gregory A Logan, William E Wixted, Jen-Pyng Kou, Diana G Chalupowicz, Heidi G Feldser, Yolanda Sanchez, Hong Nie, James F Callahan, Jeffrey K Kerns, Patricia L Podolin
Nrf2 is a key regulator of oxidative stress and cellular repair, and can be activated through inhibition of its cytoplasmic repressor, Keap1. Several small molecule disrupters of the Nrf2-Keap1 complex have recently been tested and/or approved for human therapeutic use but lack either potency or selectivity. The main goal of our work was to develop a potent, selective activator of NRF2 as protection against oxidative stress. In human bronchial epithelial cells our Nrf2 activator, PSTC, induced Nrf2 nuclear translocation, Nrf2-regulated gene expression, and downstream signaling events including induction of NQO1 enzyme activity and HO-1 protein expression, in an Nrf2-dependent manner...
August 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28783600/selenium-antagonizes-cadmium-induced-apoptosis-in-chicken-spleen-but-not-involving-nrf2-regulated-antioxidant-response
#5
Menghao Chen, Xiaojing Li, Ruifeng Fan, Changyu Cao, Haidong Yao, Shiwen Xu
The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl2, 150mg/kg) and sodium selenite (Na2SeO3, 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days...
August 4, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28767070/various-mechanisms-involve-the-nuclear-factor-erythroid-derived-2-like-nrf2-to-achieve-cytoprotection-in-long-term-cisplatin-treated-urothelial-carcinoma-cell-lines
#6
Margaretha A Skowron, Günter Niegisch, Philipp Albrecht, Gommert van Koeveringe, Andrea Romano, Peter Albers, Wolfgang A Schulz, Michèle J Hoffmann
Therapeutic efficacy of cisplatin-based chemotherapy for advanced-stage urothelial carcinoma (UC) is limited by drug resistance. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway is a major regulator of cytoprotective responses. We investigated its involvement in cisplatin resistance in long-term cisplatin treated UC cell lines (LTTs). Expression of NRF2 pathway components and targets was evaluated by qRT-PCR and western blotting in LTT sublines from four different parental cells. NRF2 transcriptional activity was determined by reporter assays and total glutathione (GSH) was quantified enzymatically...
August 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28764960/contrasting-effects-of-a-classic-nrf2-activator-tert-butylhydroquinone-on-the-glutathione-related-antioxidant-defenses-in-pacific-oysters-crassostrea-gigas
#7
Naissa Maria Danielli, Rafael Trevisan, Danielle Ferraz Mello, Kelvis Fischer, Vanessa Schadeck Deconto, Adalto Bianchini, Afonso Celso Dias Bainy, Alcir Luiz Dafre
Nrf2 is a well-known transcription factor controlling a number of antioxidant defense-related genes, which is understudied in bivalves. In this study, oysters Crassostrea gigas were exposed for 24, 48 and 96 h to 10 or 30 μM tert-butylhydroquinone (tBHQ), a classic Nrf2 activator. At 96 h, a clear induction of GSH-related antioxidant defenses was observed in gills of tBHQ-exposed animals, including GSH, glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR). Unexpectedly, the activities of GST, GPx and GR were significantly decreased 24 h after tBHQ treatment, suggesting a possible inhibition, which was supported by in vitro experiments...
July 22, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/28760781/mir-432-induces-nrf2-stabilization-by-directly-targeting-keap1
#8
Burak Akdemir, Yasuaki Nakajima, Johji Inazawa, Jun Inoue
NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the post-translational level. In human cancers, aberrantly stabilized NRF2, by the mutation of either NRF2 or KEAP1 or by the potential inhibition of autophagy, plays a vital role in tumor growth and chemoresistance through the activation of target genes. MicroRNAs (miRNAs) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with translation and/or stability of target transcripts...
July 31, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28757910/curcumin-protects-skin-against-uvb-induced-cytotoxicity-via-the-keap1-nrf2-pathway-the-use-of-a-microemulsion-delivery-system
#9
Maya Ben Yehuda Greenwald, Marina Frušić-Zlotkin, Yoram Soroka, Shmuel Ben Sasson, Ronit Bitton, Havazelet Bianco-Peled, Ron Kohen
Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28746889/molecular-recognition-between-potential-natural-inhibitors-of-the-keap1-nrf2-complex
#10
Martiniano Bello, José Antonio Morales-González
Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, which has been identified as an important approach for the prevention of different chronic diseases in which oxidative stress and inflammation are present, such as cancer, diabetes, Alzheimer's and Parkinson's. Based on the high potential to modulate antioxidant, anti-inflammatory and anticancer properties that the discovery of Keap1-Nrf2 protein-protein interaction inhibitors would represent, the utilization of some natural compounds has emerged as a promising strategy to identify new drugs...
July 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28732803/-7-s-hydroxymatairesinol-protects-against-tumor-necrosis-factor-%C3%AE-mediated-inflammation-response-in-endothelial-cells-by-blocking-the-mapk-nf-%C3%AE%C2%BAb-and-activating-nrf2-ho-1
#11
Di Yang, Chen-Xi Xiao, Zheng-Hua Su, Meng-Wei Huang, Ming Qin, Wei-Jun Wu, Wan-Wan Jia, Yi-Zhun Zhu, Jin-Feng Hu, Xin-Hua Liu
BACKGROUND: Endothelial inflammation is an increasingly prevalent condition in the pathogenesis of many cardiovascular diseases. (-)-7(S)-hydroxymatairesinol (7-HMR), a naturally occurring plant lignan, possesses both antioxidant and anti-cancer properties and therefore would be a good strategy to suppress tumor necrosis factor-α (TNF-α)-mediated inflammation in vascular endothelial cells (VECs). PURPOSE: The objective of this study is to evaluate for its anti-inflammatory effect on TNF-α-stimulated VECs and underling mechanisms...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28722304/nrf2-as-a-target-for-prevention-of-age-related-and-diabetic-cataracts-by-against-oxidative-stress
#12
REVIEW
Xiu-Fen Liu, Ji-Long Hao, Tian Xie, Tayyab Hamid Malik, Cheng-Bo Lu, Cong Liu, Chang Shu, Cheng-Wei Lu, Dan-Dan Zhou
Cataract is one of the most important causes of blindness worldwide, with age-related cataract being the most common one. Agents preventing cataract formation are urgently required. Substantial evidences point out aggravated oxidative stress as a vital factor for cataract formation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) system is considered as one of the main cellular defense mechanisms against oxidative stresses...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28719149/cadmium-induced-toxicity-is-rescued-by-curcumin-a-review
#13
REVIEW
Mohammad Mohajeri, Mehdi Rezaee, Amirhossein Sahebkar
Cadmium (Cd) is one of the most common environmental and occupational heavy metals with extended distribution. Exposure to Cd may be associated with several deleterious consequences on the liver, bones, kidneys, lungs, testes, brain, immunological, and cardiovascular systems. Overproduction of reactive oxygen species (ROS) as the main mechanism behind its toxicity causes oxidative stress and subsequent damages to lipids, proteins, and DNA. Therefore, antioxidants along with chelating agents have shown promising outcomes against Cd-induced toxicity...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28714957/il-11-contribution-to-tumorigenesis-in-an-nrf2-addiction-cancer-model
#14
H Kitamura, Y Onodera, S Murakami, T Suzuki, H Motohashi
The interaction between cancer cells and their microenvironment is an important determinant of the pathological nature of cancers, particularly their tumorigenic abilities. The KEAP1-NRF2 system, originally identified as a critical defense mechanism against oxidative stress, is often dysregulated in various human cancers forming solid tumors, resulting in the aberrant activation of NRF2. Increased accumulation of NRF2 in cancers is strongly associated with the poor prognoses of cancer patients, including those with lung and breast cancers...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28709147/7-deacetylgedunin-suppresses-inflammatory-responses-through-activation-of-keap1-nrf2-ho-1-signaling
#15
Jian-Yu Chen, Guo-Yuan Zhu, Xiao-Hui Su, Rui Wang, Juan Liu, Kangsheng Liao, Rutong Ren, Ting Li, Liang Liu
Macrophages play a critical role in a variety of inflammatory diseases. Activation of Keap1/Nrf2/HO-1 signaling results in inactivation of macrophages and amelioration of inflammatory and autoimmune conditions. Hence, discovery for the activators of Keap1/Nrf2/HO-1 signaling has become a promising strategy for treatment inflammatory diseases. In the current study, the anti-inflammatory potential of 7-deacetylgedunin (7-DGD), a limonin chemical isolated from the fruits of Toona sinensis (A. Juss.) Roem, was intensively examined in vivo and in vitro for the first time...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699353/radiation-hormesis-the-link-to-nanomolar-hydrogen-peroxide
#16
Helmut Sies, Ludwig E Feinendegen
Hydrogen peroxide (H2O2) is a stable product of water radiolysis, occurring at nanomolar concentration upon low-dose ionizing radiation (LDIR) (<100 mGy). In view of the recent recognition of H2O2 as a central redox signaling molecule that, likewise, is maintained in the nanomolar range in cells, we propose a role for H2O2 in radiation hormesis. LDIR is capable of utilizing known molecular redox master switches such as Nrf2/Keap1 or NF-κB/IκB to effect adaptive resistance. This leads to the hypothesis that, as a normal component of the exposome, LDIR mediates hormetic effects by H2O2 signaling...
August 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28697633/zinc-l-carnosine-suppresses-inflammatory-responses-in-lipopolysaccharide-induced-raw-264-7-murine-macrophages-cell-line-via-activation-of-nrf2-ho-1-signaling-pathway
#17
Theng Choon Ooi, Kok Meng Chan, Razinah Sharif
CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer. OBJECTIVE: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay...
July 11, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28693803/the-see-saw-of-keap1-nrf2-pathway-in-cancer
#18
REVIEW
Poorti Pandey, Alok Kumar Singh, Mritunjai Singh, Mallika Tewari, Hari Shankar Shukla, Indrajeet Singh Gambhir
Keap1-Nrf2 pathway is continuously involved in the cytoprotection from oxidative stress generated due to various factors either extrinsic or intrinsic in origin. This role of Nrf2 in the response to oxidative stress is well established. Following oxidative insult, Nrf2 mediates the regulation of the inducible expression of cytoprotective genes. The level and functional capacity of Nrf2 is regulated at the post-transcriptional level, mainly through its association with an actin-associated protein, Keap1. Various studies reported that any discrepancy from their routine may lead to promotion of tumor as well...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28690762/sestrin2-as-a-novel-biomarker-and-therapeutic-target-for-various-diseases
#19
REVIEW
Mazhar Pasha, Ali H Eid, Assaad A Eid, Yves Gorin, Shankar Munusamy
Sestrin2 (SESN2), a highly conserved stress-inducible metabolic protein, is known to repress reactive oxygen species (ROS) and provide cytoprotection against various noxious stimuli including genotoxic and oxidative stress, endoplasmic reticulum (ER) stress, and hypoxia. Studies demonstrate that the upregulation of Sestrin2 under conditions of oxidative stress augments autophagy-directed degradation of Kelch-like ECH-associated protein 1 (Keap1), which targets and breaks down nuclear erythroid-related factor 2 (Nrf2), a key regulator of various antioxidant genes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28684421/pharmacological-stimulation-of-nuclear-factor-erythroid-derived-2-like-2-translation-activates-antioxidant-responses
#20
Oscar Perez-Leal, Carlos Alberto Barrero, Salim Merali
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcriptional, translational, and post- translational levels. It is well known that Nrf2 is regulated at the protein level by proteasomal degradation via Kelch-like ECH-associated protein 1 (Keap1), but how Nrf2 is regulated at the translational level is less clear. Here, we show that pharmacological stimulation increases Nrf2 levels by overcoming basal translational repression...
July 6, 2017: Journal of Biological Chemistry
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