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https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#1
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28216009/upregulating-nrf2-dependent-antioxidant-defenses-in-pacific-oysters-crassostrea-gigas-investigating-the-nrf2-keap1-pathway-in-bivalves
#2
Naissa Maria Danielli, Rafael Trevisan, Danielle Ferraz Mello, Kelvis Fischer, Vanessa Schadeck Deconto, Daiane da Silva Acosta, Adalto Bianchini, Afonso C D Bainy, Alcir Luiz Dafre
Analysis of the Pacific oyster Crassostrea gigas annotated genome revealed genes with conserved sequences belonging to typical cap 'n' collar Nrf2 domain, a major player in antioxidant protection, and domains belonging to Nrf2 cytoplasmic repressor (Keap1), but little is known about Nrf2/Keap1 induction in bivalves. C. gigas were exposed to waterborne 10 and 30μM curcumin, a known inducer of the mammalian Nrf2. Curcumin disappeared from the seawater after 10h, and accumulated in the gills (10h) and digestive gland (10-96h)...
February 12, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28213287/butein-induction-of-ho-1-by-p38-mapk-nrf2-pathway-in-adipocytes-attenuates-high-fat-diet-induced-adipose-hypertrophy-in-mice
#3
Zheng Wang, Sun-O Ka, Youngyi Lee, Byung-Hyun Park, Eun Ju Bae
Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2)...
February 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28202604/retraction-antioxidant-induced-inrf2-keap1-tyrosine-85-phosphorylation-controls-the-nuclear-export-and-degradation-of-the-inrf2-cul3-rbx1-complex-to-allow-normal-nrf2-activation-and-repression
#4
James W Kaspar, Suryakant K Niture, Anil K Jaiswal
No abstract text is available yet for this article.
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#5
Hongming Lv, Qinmei Liu, Junfeng Zhou, Guangyun Tan, Xuming Deng, Xinxin Ci
Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28186440/britanin-ameliorates-cerebral-ischemia-reperfusion-injury-by-inducing-the-nrf2-protective-pathway
#6
Guozhen Wu, Lili Zhu, Xing Yuan, Hao Chen, Rui Xiong, Shoude Zhang, Hao Cheng, Yunheng Shen, Huazhang An, Tiejun Li, Honglin Li, Weidong Zhang
AIMS: Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. RESULTS: The herb-derived compound Britanin is a potent inducer of the Nrf2 system...
February 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28178212/anti-inflammatory-activity-of-sanghuangporus-sanghuang-mycelium
#7
Wang-Ching Lin, Jeng-Shyan Deng, Shyh-Shyun Huang, Sheng-Hua Wu, Chin-Chu Chen, Wan-Rong Lin, Hui-Yi Lin, Guan-Jhong Huang
Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28168414/the-anti-aging-effect-of-erythropoietin-via-the-erk-nrf2-are-pathway-in-aging-rats
#8
Haiqin Wu, Jiaxin Zhao, Mengyi Chen, Huqing Wang, Qingling Yao, Jiaxin Fan, Meng Zhang
Erythropoietin (EPO) has a neuroprotective effect and can resist aging, which most likely occur through EPO increasing the activity of antioxidant enzymes and scavenging free radicals. In this study, we verified the anti-aging function of EPO and discussed the mechanism occurring through the extracellular signal-regulated kinase (ERK)/NF-E2-related factor 2 (Nrf2)-ARE pathway. A rat model of aging was induced by the continuous subcutaneous injection of 5 % D-galactose for 6 weeks. At the beginning of the sixth week, physiological saline or EPO was administered twice per day through a lateral ventricle system for a total of 7 days...
February 6, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28157180/toxic-metabolites-mapk-and-nrf2-keap1-signaling-pathways-involved-in-oxidative-toxicity-in-mice-liver-after-chronic-exposure-to-mequindox
#9
Qianying Liu, Zhixin Lei, Anxiong Huang, Qinghua Wu, Shuyu Xie, Ihsan Awais, Menghong Dai, Xu Wang, Zonghui Yuan
Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28149633/keap1-nrf2-impairing-revised-are-we-missing-the-single-nucleotide-polymorphisms
#10
COMMENT
Lucia Anna Muscarella, Vito Michele Fazio
No abstract text is available yet for this article.
December 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28145866/keap1-loss-modulates-sensitivity-to-kinase-targeted-therapy-in-lung-cancer
#11
Elsa B Krall, Belinda Wang, Diana M Munoz, Nina Ilic, Srivatsan Raghavan, Matthew J Niederst, Kristine Yu, David A Ruddy, Andrew J Aguirre, Jong Wook Kim, Amanda J Redig, Justin F Gainor, Juliet A Williams, John M Asara, John G Doench, Pasi A Janne, Alice T Shaw, Robert E McDonald Iii, Jeffrey A Engelman, Frank Stegmeier, Michael R Schlabach, William C Hahn
Inhibitors that target the receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) pathway have led to clinical responses in lung and other cancers, but some patients fail to respond and in those that do resistance inevitably occurs (Balak et al., 2006; Kosaka et al., 2006; Rudin et al., 2013; Wagle et al., 2011). To understand intrinsic and acquired resistance to inhibition of MAPK signaling, we performed CRISPR-Cas9 gene deletion screens in the setting of BRAF, MEK, EGFR, and ALK inhibition...
February 1, 2017: ELife
https://www.readbyqxmd.com/read/28145852/safranal-prevents-rotenone-induced-oxidative-stress-and-apoptosis-in-an-in-vitro-model-of-parkinson-s-disease-through-regulating-keap1-nrf2-signaling-pathway
#12
P-K Pan, L-Y Qiao, X-N Wen
Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenone-induced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28129239/expression-patterns-of-nrf2-and-keap1-in-ovarian-cancer-cells-and-their-prognostic-role-in-disease-recurrence-and-patient-survival
#13
Hye-Yon Cho, Kidong Kim, Yong-Beom Kim, Haeryoung Kim, Jae Hong No
OBJECTIVE: This study evaluated the expression patterns of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) and assessed their clinical value as prognostic indicators in ovarian cancer. METHODS: The expression patterns of Nrf2 and Keap1 were determined in 100 epithelial ovarian cancers by immunohistochemistry analyses. The associations of Nrf2 and Keap1 expression with clinicopathological characteristics of patients were evaluated...
March 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28128368/computational-design-of-an-epitope-specific-keap1-binding-antibody-using-hotspot-residues-grafting-and-cdr-loop-swapping
#14
Xiaofeng Liu, Richard D Taylor, Laura Griffin, Shu-Fen Coker, Ralph Adams, Tom Ceska, Jiye Shi, Alastair D G Lawson, Terry Baker
Therapeutic and diagnostic applications of monoclonal antibodies often require careful selection of binders that recognize specific epitopes on the target molecule to exert a desired modulation of biological function. Here we present a proof-of-concept application for the rational design of an epitope-specific antibody binding with the target protein Keap1, by grafting pre-defined structural interaction patterns from the native binding partner protein, Nrf2, onto geometrically matched positions of a set of antibody scaffolds...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126440/activation-of-anti-oxidant-nrf2-signaling-by-substituted-trans-stilbenes
#15
Lorraine M Deck, Lisa J Whalen, Lucy A Hunsaker, Robert E Royer, David L Vander Jagt
Nrf2, which is a member of the cap'n'collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation of anti-oxidant Nrf2 signaling may have therapeutic potential. A number of Nrf2 activators have entered into clinical trials. Nrf2 exists in the cytosol in complex with its binding partner Keap1, which is a thiol-rich redox-sensing protein...
January 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28123399/the-status-of-nrf2-based-therapeutics-current-perspectives-and-future-prospects
#16
REVIEW
Irina G Gazaryan, Bobby Thomas
This mini-review presents the authors' vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. There are two opposite "chemical" mechanisms underlying such activation: the first one is a non-specific covalent modification of Keap1 thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28118364/physical-and-flavor-characteristics-fatty-acid-profile-antioxidant-status-and-nrf2-dependent-antioxidant-enzyme-gene-expression-changes-in-young-grass-carp-ctenopharyngodon-idella-fillets-fed-dietary-valine
#17
Jian-Bo Luo, Lin Feng, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study was conducted to examine the effects of dietary valine on the physical and flavor characteristics, fatty acid (FA) profile, antioxidant status and Nrf2-dependent antioxidant enzyme gene expression in the muscle of young grass carp (Ctenopharyngodon idella) fed increasing levels of valine (4.3, 8.0, 10.6, 13.1, 16.9 and 19.1 g/kg) for 8 weeks. Compared with the control group, the group fed valine showed improved physical characteristics of fish fillets (increased relative shear force, hydroxyproline, protein and lipid levels and decreased cathepsin B and L activities, as well as cooking loss, were observed)...
2017: PloS One
https://www.readbyqxmd.com/read/28115850/gold-quercetin-nanoparticles-prevent-metabolic-endotoxemia-induced-kidney-injury-by-regulating-tlr4-nf-%C3%AE%C2%BAb-signaling-and-nrf2-pathway-in-high-fat-diet-fed-mice
#18
Min-Xuan Xu, Ming Wang, Wei-Wei Yang
High-fat diet-induced metabolic syndrome followed by chronic kidney disease caused by intestinal endotoxemia have received extensive attention. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and oxidative stress-related Nrf2/Keap1 were regarded as the key target points involved in metabolic inflammation and kidney injury. However, the molecular mechanism of interaction between TLR4/NF-κB and Nrf2 activation in high-fat diet-induced renal injury is not absolutely understood. Quercetin, a natural product, has been reported to possess antitumor and anti-inflammatory effects...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28115426/p97-negatively-regulates-nrf2-by-extracting-ubiquitylated-nrf2-from-the-keap1-cul3-e3-complex
#19
Shasha Tao, Pengfei Liu, Gang Luo, Montserrat Rojo de la Vega, Heping Chen, Tongde Wu, Joseph Tillotson, Eli Chapman, Donna D Zhang
Activation of the stress responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and targeted to the proteasome for degradation (the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation had been previously unknown. p97 is an ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system (UPS)...
January 23, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28110218/hydrogen-peroxide-as-a-central-redox-signaling-molecule-in-physiological-oxidative-stress-oxidative-eustress
#20
REVIEW
Helmut Sies
Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H2O2 in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of H2O2 and on the role of H2O2 in redox signaling under physiological conditions (1-10nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB...
January 5, 2017: Redox Biology
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