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https://www.readbyqxmd.com/read/28515676/low-dose-dose-response-for-in-vitro-nrf2-are-activation-in-human-hepg2-cells
#1
Kenneth T Bogen
Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-like factor 2-related factor 2 (Nrf2), and the antioxidant response element (ARE) are interacting components of a master regulatory signaling pathway that coordinates redox homeostasis, cytoprotective responses, and shifts in stem cell state. This study reexamined detailed dose-response (DR) data reported for in vitro Nrf2-ARE activation in human hepatoblastoma HepG2 cell lines containing either a ARE-bla or ARE-luc reporter at 12 different concentrations of each of 15 chemicals...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28515152/effects-of-deficiency-of-kelch-like-ech-associated-protein-1-on-skeletal-organization-a-mechanism-for-diminished-nuclear-factor-of-activated-t-cells-cytoplasmic-1-during-osteoclastogenesis
#2
Eiko Sakai, Masanobu Morita, Masahiro Ohuchi, Mizuho A Kido, Yutaka Fukuma, Kazuhisa Nishishita, Kuniaki Okamoto, Ken Itoh, Masayuki Yamamoto, Takayuki Tsukuba
Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor E2 p45-related factor 2 (Nrf2), a transcription factor for antioxidant enzymes, to suppress Nrf2 activation. The role of oxidative stress in many diseases supports the possibility that processes that are associated with Nrf2 activation might offer therapeutic potential. Nrf2 deficiency induces osteoclastogenesis, which is responsible for bone loss, by activating receptor activator of NF-κB ligand (RANKL)-mediated signaling; however, the effects of Keap1 deficiency remain unclear...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28510041/the-keap1-nrf2-pathway-promising-therapeutic-target-to-counteract-ros-mediated-damage-in-cancers-and-neurodegenerative-diseases
#3
REVIEW
Prashant Deshmukh, Sruthi Unni, Gopinatha Krishnappa, Balasundaram Padmanabhan
The overproduction of reactive oxygen species (ROS) generates oxidative stress in cells. Oxidative stress results in various pathophysiological conditions, especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2 [Kelch-like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2] regulatory pathway plays a central role in protecting cells against oxidative and xenobiotic stresses. The Nrf2 transcription factor activates the transcription of several cytoprotective genes that have been implicated in protection from cancer and NDD...
February 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28507037/systemic-activation-of-nrf2-alleviates-lethal-autoimmune-inflammation-in-scurfy-mice
#4
Takuma Suzuki, Shohei Murakami, Shyam S Biswal, Shimon Sakaguchi, Hideo Harigae, Masayuki Yamamoto, Hozumi Motohashi
The transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2) plays crucial roles in the defense mechanisms against oxidative stress and mediates anti-inflammatory actions in various pathological conditions. Recent studies have shown that the dysfunction of regulatory T cells (Tregs) is directly linked to the initiation and progression of various autoimmune diseases. To determine the Treg-independent impact of NRF2 activation on autoimmune inflammation, we examined Scurfy (Sf) mice that are deficient in Tregs and succumb to severe multi-organ inflammation by 4 weeks of age...
May 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28504720/a-clinical-drug-library-screen-identifies-clobetasol-propionate-as-an-nrf2-inhibitor-with-potential-therapeutic-efficacy-in-keap1-mutant-lung-cancer
#5
E-J Choi, B-J Jung, S-H Lee, H-S Yoo, E-A Shin, H-J Ko, S Chang, S-Y Kim, S-M Jeon
The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28503850/roles-of-spermine-in-modulating-the-antioxidant-status-and-nrf2-signalling-molecules-expression-in-the-thymus-and-spleen-of-suckling-piglets-new-insight
#6
W Cao, X Xu, G Jia, H Zhao, X Chen, C Wu, J Tang, J Wang, J Cai, G Liu
This study aimed to investigate the effects of spermine and extended spermine administration on the antioxidant status and expression of NF-E2-related factor 2 (Nrf2) signalling molecules in the thymus and spleen in suckling piglets. One half of eighty 12-day-old suckling piglets obtained sufficient nutrient intake supplemented with spermine (0.4 mmol/kg body weight), and another half received restricted nutrient intake supplemented with physiological saline in equal doses once a day for 7 hr or 3, 6 or 9 days in pairs...
May 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28502971/targeting-the-keap1-nrf2-system-to-prevent-kidney-disease-progression
#7
Masahiro Nezu, Norio Suzuki, Masayuki Yamamoto
BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor for the antioxidative stress response and it activates a variety of cytoprotective genes related to redox and detoxification. NRF2 activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH-associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2 system has been proposed to be a therapeutic target for renal protection...
May 13, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28457936/epigallocatechin-gallate-upregulates-nrf2-to-prevent-diabetic-nephropathy-via-disabling-keap1
#8
Weixia Sun, Xiuxia Liu, Haifeng Zhang, Yanyan Song, Tie Li, Xiaona Liu, Yanze Liu, Le Guo, Fuchun Wang, Ting Yang, Weiying Guo, Junduo Wu, Hang Jin, Hao Wu
Epigallocatechin gallate (EGCG) is the most abundant and effective green tea catechin and has been reported to attenuate diabetic nephropathy (DN). However, the mechanism by which EGCG ameliorates DN, till now, has remained unclear. EGCG is known as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defense against diabetes-induced oxidative stress and in the prevention of DN. In the present study, we tested whether NRF2 is required for EGCG protection against DN...
April 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28442598/ethylene-regulates-differential-growth-via-big-arf-gef-dependent-post-golgi-secretory-trafficking-in-arabidopsis
#9
Kristoffer Jonsson, Yohann Boutté, Rajesh Kumar Singh, Delphine Gendre, Rishikesh Bhalerao
During early seedling development, the shoot apical meristem is protected from damage as the seedling emerges from soil by the formation of apical hook. Hook formation requires differential growth across the epidermis below the meristem in the hypocotyl. The plant hormones ethylene and auxin play key roles during apical hook development by controlling differential growth. We provide genetic and cell biological evidence for the role of ADP-ribosylation factor 1 (ARF1)-GTPase and its effector ARF-guanine-exchange factors (GEF)s of the BFA-inhibited GEF (BIG) family and GNOM in ethylene- and auxin-mediated control of hook development...
April 24, 2017: Plant Cell
https://www.readbyqxmd.com/read/28432761/protein-s-sulfhydration-by-hydrogen-sulfide-in-cardiovascular-system
#10
REVIEW
Guoliang Meng, Shuang Zhao, Liping Xie, Yi Han, Yong Ji
Hydrogen sulfide (H2 S), independent on any specific transporters, plays a number of biological effects on cardiovascular systems. However, the detailed mechanism of H2 S is not yet clear until now. Recently, a novel post-translational modification induced by H2 S, named S-sulfhydration, has been proposed. S-sulfhydration is a chemical modification on specific cysteine residues of target proteins by H2 S. There are several methods for S-sulfhydration detection, such as modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432440/application-of-recombinant-pediococcus-acidilactici-bd16-fcs-ech-for-bioconversion-of-agrowaste-to-vanillin
#11
Debkumar Chakraborty, Ammaiyappan Selvam, Baljinder Kaur, Jonathan Woon Chung Wong, Obulisamy Parthiba Karthikeyan
Biotechnological production of vanillin is gaining momentum as the natural synthesis of vanillin that is very expensive. Ferulic acid (FA), a costly compound, is used as the substrate to produce vanillin biotechnologically and the making process is still expensive. Therefore, this study investigated the practical use of an agrobiomass waste, rice bran, and provides the first evidence of a cost-effective production of vanillin within 24 h of incubation using recombinant Pediococcus acidilactici BD16 (fcs (+)/ech (+))...
April 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#12
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28415030/contradictory-roles-of-nrf2-keap1-signaling-pathway-in-cancer-prevention-promotion-and-chemoresistance
#13
REVIEW
Farhad Jeddi, Narges Soozangar, Mohammad Reza Sadeghi, Mohammad Hossein Somi, Nasser Samadi
NF-E2-related factor 2 (Nrf2) protein is a cytosolic transcription factor that regulates antioxidant and stress-related enzymes. Kelch-like ECH-associated protein 1 (Keap1) binds Nrf2 and accelerates ubiquitination and proteasome-dependent degradation of Nrf2. Nrf2 modifies the sensitivity of the cell environment to electrophiles and oxidants by inducing the transcriptional activation of more than 100 detoxification and cytoprotective genes. Prior investigations have found documentary evidence indicating that temporary activation of Nrf2 by pharmaceutical inducers plays a protective role against cancer initiation in normal cells...
April 3, 2017: DNA Repair
https://www.readbyqxmd.com/read/28413007/a-homozygous-keap1-knockout-human-embryonic-stem-cell-line-generated-using-crispr-cas9-mediates-gene-targeting
#14
So-Jung Kim, Omer Habib, Jin-Soo Kim, Hyo-Won Han, Soo Kyung Koo, Jung-Hyun Kim
Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28408149/leptinotarsa-cap-n-collar-isoform-c-kelch-like-ech-associated-protein%C3%A2-1-signaling-is-critical-for-the-regulation-of-ecdysteroidogenesis-in-the-larvae
#15
Qiang-Kun Sun, Qing-Wei Meng, Qing-Yu Xu, Pan Deng, Wen-Chao Guo, Guo-Qing Li
Drosophila cap 'n' collar isoform C (CncC) and Kelch-like ECH associated protein 1 (Keap1) regulate metamorphosis by transcriptional control of a subset of genes involved in ecdysteroidogenesis, 20-hydroxyecdysone (20E) signaling, and juvenile hormone (JH) degradation. In the present paper, we found that prothoracicotropic hormone signal was required for the activation of LdCncC and LdKeap1 in Leptinotarsa decemlineata. Moreover, RNA interference of LdCncC or LdKeap1 in the fourth-instar larvae delayed development...
April 10, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28377796/redox-regulating-enzymes-and-connected-microrna-regulators-have-prognostic-value-in-classical-hodgkin-lymphomas
#16
Peeter Karihtala, Katja Porvari, Ylermi Soini, Kirsi-Maria Haapasaari
There are no previous studies assessing the microRNAs that regulate antioxidant enzymes in Hodgkin lymphomas (HLs). We determined the mRNA levels of redox regulating enzymes peroxiredoxins (PRDXs) I-III, manganese superoxide dismutase (MnSOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) from a carefully collected set of 41 classical HL patients before receiving any treatments. The levels of redoxmiRs, miRNAs known to regulate the above-mentioned enzymes, were also assessed, along with CD3, CD20, and CD30 protein expression...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28373747/andrographolide-activates-keap1-nrf2-are-ho-1-pathway-in-ht22-cells-and-suppresses-microglial-activation-by-a%C3%AE-42-through-nrf2-related-inflammatory-response
#17
Ji Yeon Seo, Euisun Pyo, Jin-Pyo An, Jinwoong Kim, Sang Hyun Sung, Won Keun Oh
Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (Aβ)42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB)-mediated inflammatory responses...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28351537/determination-of-chlorinated-volatile-organic-compounds-in-polyamine-epichlorohydrin-solution-by-headspace-gas-chromatography
#18
Ning Yan, Xiao-Fang Wan, Xin-Sheng Chai, Run-Quan Chen
This study demonstrated a headspace gas chromatographic (HS-GC) method for the determination of residual epichlorohydrin (ECH) and the by-product 1,3-dichloro-2-propanol (DCP) in polyamine epichlorohydrin (PAE) solution. It was based on the vapor-liquid phase equilibrium of these analytes at 60°C for 30min in a closed headspace sample vial before GC measurement. It was found that matrix of the PAE solution had the effect on the headspace equilibrium of these species and therefore a standard addition must be applied in the method validation...
May 5, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28350063/antioxidant-and-cytoprotective-effects-of-morin-against-hydrogen-peroxide-induced-oxidative-stress-are-associated-with-the-induction-of-nrf-2%C3%A2-mediated-ho-1-expression-in-v79-4-chinese-hamster-lung-fibroblasts
#19
Moon Hee Lee, Hee-Jae Cha, Eun Ok Choi, Min Ho Han, Sung Ok Kim, Gi-Young Kim, Su Hyun Hong, Cheol Park, Sung-Kwon Moon, Soon-Jeong Jeong, Moon-Jin Jeong, Wun-Jae Kim, Yung Hyun Choi
Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)‑like activity and 2,2'‑azino‑bis‑(3‑ethylbenzothiazoline‑6‑sulfonic acid) (ABTS•+) radical scavenging activity were determined...
January 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28349780/ganoderic-acid-targeting-nuclear-factor-erythroid-2-related-factor-2-in-lung-cancer
#20
Balraj Singh Gill, Sanjeev Kumar, Navgeet
Lung cancer causes huge mortality worldwide, and targeting new pathway may provide an alternative in modulating signaling in cancer. Nuclear factor erythroid 2-related factor 2 is the major regulator of endogenous and exogenous stress by activating numerous antioxidant genes critical in cancer, Alzheimer's, Parkinson's, and inflammatory bowel diseases. Ganoderic acid is a triterpene from basiodiomycetes fungus Ganoderma lucidum with numerous therapeutic effects. In this study, ganoderic acid and its 50 isomers and natural activators were docked by receptor-based molecular docking using Maestro 9...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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