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https://www.readbyqxmd.com/read/28542357/the-nrf2-transcription-factor-plays-a-dual-role-in-colorectal-cancer-a-systematic-review
#1
C Gonzalez-Donquiles, J Alonso-Molero, T Fernandez-Villa, L Vilorio-Marqués, A J Molina, V Martín
BACKGROUND: Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2. OBJECTIVES: The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search...
2017: PloS One
https://www.readbyqxmd.com/read/28539891/double-knockdown-of-phd1-and-keap1-attenuated-hypoxia-induced-injuries-in-hepatocytes
#2
Jing Liu, Yiping Li, Lei Liu, Zhi Wang, Chuanbing Shi, Zhengyuan Cheng, Xiaoyi Zhang, Fengan Ding, Ping Sheng Chen
Background and Aims: Hypoxia and oxidative stress contribute toward liver fibrosis. In this experiment, we used small hairpin RNA (shRNA) to interfere with the intracellular oxygen sensor-prolyl hydroxylase 1 (PHD1) and the intracellular oxidative stress sensor-kelch-like ECH associated protein 1 (Keap1) in the hypoxic hepatocytes in order to investigate the function of PHD1and Keap1. Methods: We first established the CCl4-induced liver fibrosis model, subsequently, the levels of the PHD1, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), Keap1, and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) were detected in liver tissues...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28534518/cdk20-interacts-with-keap1-to-activate-nrf2-and-promotes-radiochemoresistance-in-lung-cancer-cells
#3
Q Wang, J Ma, Y Lu, S Zhang, J Huang, J Chen, J-X Bei, K Yang, G Wu, K Huang, J Chen, S Xu
Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533375/keap1-modifying-small-molecule-reveals-muted-nrf2-signaling-responses-in-neural-stem-cells-from-huntington-s-disease-patients
#4
Luisa Quinti, Sharadha Dayalan Naidu, Ulrike Träger, Xiqun Chen, Kimberly Kegel-Gleason, David Llères, Colúm Connolly, Vanita Chopra, Cho Low, Sébastien Moniot, Ellen Sapp, Adelaide R Tousley, Petr Vodicka, Michael J Van Kanegan, Linda S Kaltenbach, Lisa A Crawford, Matthew Fuszard, Maureen Higgins, James R C Miller, Ruth E Farmer, Vijay Potluri, Susanta Samajdar, Lisa Meisel, Ningzhe Zhang, Andrew Snyder, Ross Stein, Steven M Hersch, Lisa M Ellerby, Eranthie Weerapana, Michael A Schwarzschild, Clemens Steegborn, Blair R Leavitt, Alexei Degterev, Sarah J Tabrizi, Donald C Lo, Marian DiFiglia, Leslie M Thompson, Albena T Dinkova-Kostova, Aleksey G Kazantsev
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532831/cryosurvival-of-in%C3%A2-vitro-produced-bovine-embryos-supplemented-with-l-carnitine-and-concurrent-reduction-of-fatty-acids
#5
E Held-Hoelker, S L Klein, F Rings, D Salilew-Wondim, M Saeed-Zidane, C Neuhoff, D Tesfaye, K Schellander, M Hoelker
Lipid accumulation is associated with reduced embryonic quality, causing limited survival after cryopreservation. Therefore, in the present study we aimed to reveal the effects of supplementation of a lipid reducing agent, l-carnitine and the removal of fatty acids during in vitro culture on the morphological as well as on the molecular level. To accomplish that, presumptive zygotes were cultured in 4 contrasting groups: namely SOFaa medium supplemented with BSA, (BSA), SOFaa medium supplemented with fatty acid free BSA (FAF), SOFaa medium supplemented with BSA as well as l-Carnitine (BSA + LC) and SOFaa medium concurrently supplemented with fatty acid free BSA and l-Carnitine (FAF + LC)...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28523248/the-keap1-nrf2-system-in-cancer
#6
REVIEW
Keiko Taguchi, Masayuki Yamamoto
Cancer cells first adapt to the microenvironment and then propagate. Mutations in tumor suppressor genes or oncogenes are frequently found in cancer cells. Comprehensive genomic analyses have identified somatic mutations and other alterations in the KEAP1 or NRF2 genes and in well-known tumor suppressor genes or oncogenes, such as TP53, CDKN2A, PTEN, and PIK3CA, in various types of cancer. Aberrant NRF2 activation in cancer cells occurs through somatic mutations in the KEAP1 or NRF2 gene as well as through other mechanisms that disrupt the binding of KEAP1 to NRF2...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28522909/in-vitro-and-in-vivo-antioxidative-and-hepatoprotective-activity-of-aqueous-extract-of-cortex-dictamni
#7
Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Hiderori Arai, Yang Xu
AIM: To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4)-induced liver damage in rats. METHODS: The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28515676/low-dose-dose-response-for-in-vitro-nrf2-are-activation-in-human-hepg2-cells
#8
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
#9
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/28514495/protective-effects-of-dioscin-against-cisplatin-induced-nephrotoxicity-via-regulating-mir-34a-sirt1-signal-pathway
#10
Yimeng Zhang, Xufeng Tao, Lianhong Yin, Lina Xu, Youwei Xu, Yan Qi, Xu Han, Shasha Song, Yanyan Zhao, Yuan Lin, Kexin Liu, Jinyong Peng
BACKGROUND AND PURPOSE: Dioscin has various pharmacological actions in our previous works, however, little is known concerning the role of it on cisplatin (CDDP)-induced nephrotoxicity. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against CDDP-induced nephrotoxicity. EXPERIMENTAL APPROACH: In the present study, the in vivo models of CDDP-induced nephrotoxicity in rats and mice were used, and the in vitro models on NRK-52E and HK-2 cells were developed...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28512147/nrf2-inactivation-enhances-placental-angiogenesis-in-a-preeclampsia-mouse-model-and-improves-maternal-and-fetal-outcomes
#11
Masahiro Nezu, Tomokazu Souma, Lei Yu, Hiroki Sekine, Nobuyuki Takahashi, Andrew Zu-Sern Wei, Sadayoshi Ito, Akiyoshi Fukamizu, Zsuzsanna K Zsengeller, Tomohiro Nakamura, Atsushi Hozawa, S Ananth Karumanchi, Norio Suzuki, Masayuki Yamamoto
Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage...
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28510041/the-keap1-nrf2-pathway-promising-therapeutic-target-to-counteract-ros-mediated-damage-in-cancers-and-neurodegenerative-diseases
#12
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
#13
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
#14
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
#15
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
#16
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/28494652/the-keap1-nrf2-stress-response-pathway-promotes-mitochondrial-hyperfusion-through-degradation-of-the-mitochondrial-fission-protein-drp1
#17
Rasha Sabouny, Erik Fraunberger, Michèle Geoffrion, Andy Ng, Stephen Baird, Robert Screaton, Ross Milne, Heidi M McBride, Tim Shutt
AIMS: Mitochondrial function is coupled to metabolic and survival pathways through both direct signaling cascades and dynamic changes in mitochondrial morphology. For example, a hyperfused mitochondrial reticulum is activated upon cellular stress and is protective against cell death. As part of a genome-wide siRNA screen, we identified the central redox regulator, Keap1 as a novel regulator of mitochondrial morphology. Here, we aimed to determine the mechanism through which redox signaling and Keap1 mediates changes in mitochondrial morphology...
May 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28482326/constitutive-activation-of-nrf2-induces-a-stable-reductive-state-in-the-mouse-myocardium
#18
Gobinath Shanmugam, Madhusudhanan Narasimhan, Susan Tamowski, Victor Darley-Usmar, Namakkal S Rajasekaran
Redox homeostasis regulates key cellular signaling pathways in both physiology and pathology. The cell's antioxidant response provides a defense against oxidative stress and establishes a redox tone permissive for cell signaling. The molecular regulation of the well-known Keap1/Nrf2 system acts as sensor responding to changes in redox homeostasis and is poorly studied in the heart. Importantly, it is not yet known whether Nrf2 alone can serve as a master regulator of cellular redox homeostasis without compensation of the transcriptional regulation of antioxidant response element (ARE) genes through alternate mechanisms...
May 3, 2017: Redox Biology
https://www.readbyqxmd.com/read/28473877/involvement-of-nrf2-in-ocular-diseases
#19
REVIEW
Shehzad Batliwala, Christy Xavier, Yang Liu, Hongli Wu, Iok-Hou Pang
The human body harbors within it an intricate and delicate balance between oxidants and antioxidants. Any disruption in this checks-and-balances system can lead to harmful consequences in various organs and tissues, such as the eye. This review focuses on the effects of oxidative stress and the role of a particular antioxidant system-the Keap1-Nrf2-ARE pathway-on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Together, they are the major causes of blindness in the world...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28473247/oxidized-5-aminosalicylic-acid-activates-nrf2-ho-1-pathway-by-covalently-binding-to-keap1-implication-in-anti-inflammatory-actions-of-5-aminosalicylic-acid
#20
Sookjin Kang, Wooseong Kim, Seongkeun Jeong, Yonghyun Lee, Joon Nam, Sunyoung Lee, Yunjin Jung
Mesalazine (5-aminosalicylic acid, 5-ASA), a currently used drug for anti-inflammatory bowel disease, is easily oxidized by HOCl, a strong oxidant generated in gut inflammation, to produce electrophilic quinones. We investigated whether this chemical feature has an implication in the anti-inflammatory pharmacology of 5-ASA. Human colon carcinoma HCT116 cells were treated with HOCl-reacted 5-ASA. Oxidized 5-ASA activated Nrf2 while 5-ASA itself was not effective. Activation of Nrf2 led to induction of hemeoxygenase (OH)-1, an anti-inflammatory enzyme...
May 1, 2017: Free Radical Biology & Medicine
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