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https://www.readbyqxmd.com/read/28427912/hepataprotective-effects-of-ginsenoside-rg1-a-review
#1
REVIEW
Yan Gao, Shifeng Chu, Zhao Zhang, Naihong Chen
BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng has been used as efficient tonic and for the treatment of various diseases including hepatic disorders. Ginseng saponins, also known as ginsenosides, are principal constituents and have been treated to be responsible for disparate ginseng health benefits. The current review mainly focuses on ginsenoside Rg1, a compound isolated from traditional Chinese herbal medicine Panax ginseng Meyer. AIMS: To summary the hepataprotective effects and related mechanisms of ginsenoside Rg1, we conclude this review by combining the literature and our own researches...
April 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28416489/nrf2-induction-supporting-breast-cancer-cell-survival-is-enabled-by-oxidative-stress-induced-dpp3-keap1-interaction
#2
Kevin Lu, Allen L Alcivar, Jianglin Ma, Tzeh K Foo, Susan Zwyea, Amar Mahdi, Yanying Huo, Thomas W Kensler, Michael L Gatza, Bing Xia
NRF2 is a transcription factor serving as a master regulator of the expression of many genes involved in cellular responses to oxidative and other stresses. In the absence of stress, NRF2 is constantly synthesized but maintained at low levels as it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation. NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found in several other proteins, such as DPP3, which has been shown to bind KEAP1 and enhance NRF2 function upon overexpression...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416257/nrf2-and-regulation-of-the-antioxidant-system-in-the-antarctic-silverfish-pleuragramma-antarctica-adaptation-to-environmental-changes-of-pro-oxidant-pressure
#3
Maria Elisa Giuliani, Maura Benedetti, Marco Nigro, Francesco Regoli
Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in vertebrates, this system is still poorly investigated in marine species. The present study focused on the Antarctic silverfish Pleuragramma antarctica which, during the final phases of embryo development in platelet ice, is challenged by a sudden enhancement of environmental oxidative conditions associated to ice melting. Partial coding sequences were identified for Nrf2, its repressor Keap1 and for typical Nrf2-target antioxidant genes, like catalase, glutathione peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase...
April 7, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/28415030/contradictory-roles-of-nrf2-keap1-signaling-pathway-in-cancer-prevention-promotion-and-chemoresistance
#4
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
#5
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/28411557/controversy-about-pharmacological-modulation-of-nrf2-for-cancer-therapy
#6
REVIEW
Lidija Milkovic, Neven Zarkovic, Luciano Saso
Conventional anticancer therapies such as radiotherapy and chemotherapies are associated with oxidative stress generating reactive oxygen species (ROS) and reactive aldehydes like 4-hydroxynonenal in cancer cells that govern them to die. The main mechanism activated due to exposure of the cell to these reactive species is the Nrf2-Keap1 pathway. Although Nrf2 was firstly perceived as a tumor suppressor that inhibits tumor initiation and cancer metastasis, more recent data reveal its role also as a pro-oncogenic factor...
April 8, 2017: Redox Biology
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
#7
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/28391065/novel-lipoproteoplex-delivers-keap1-sirna-based-gene-therapy-to-accelerate-diabetic-wound-healing
#8
Piul S Rabbani, Anna Zhou, Zachary M Borab, Joseph A Frezzo, Nikita Srivastava, Haresh T More, William J Rifkin, Joshua A David, Samuel J Berens, Raymond Chen, Sophia Hameedi, Muhammad H Junejo, Camille Kim, Rita A Sartor, Che F Liu, Pierre B Saadeh, Jin K Montclare, Daniel J Ceradini
Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC)...
April 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28382390/protective-effect-of-glutamine-on-the-main-and-adjacent-organs-damaged-by-ischemia-reperfusion-in-rats
#9
Renata Minuzzo Hartmann, Francielli Licks, Elizângela Gonçalves Schemitt, Josieli Raskopf Colares, Mariana do Couto Soares, Gilmara Pandolfo Zabot, Henrique Sarubbi Fillmann, Norma Possa Marroni
Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300 g) were divided into four groups: sham-operated (SO), glutamine + SO (G + SO), I/R, and glutamine + I/R (G + I/R)...
April 5, 2017: Protoplasma
https://www.readbyqxmd.com/read/28380357/keap1-cullin3-modulates-p62-sqstm1-activity-via-uba-domain-ubiquitination
#10
YouJin Lee, Tsui-Fen Chou, Sara K Pittman, Amy L Keith, Babak Razani, Conrad C Weihl
p62/SQSTM1 (p62) is a scaffolding protein that facilitates the formation and degradation of ubiquitinated aggregates via its self-interaction and ubiquitin binding domains. The regulation of this process is unclear but may relate to the post-translational modification of p62. In the present study, we find that Keap1/Cullin3 ubiquitinates p62 at lysine 420 within its UBA domain. Substitution of lysine 420 with an arginine diminishes p62 sequestration and degradation activity similar what is seen when the UBA domain is deleted...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28377796/redox-regulating-enzymes-and-connected-microrna-regulators-have-prognostic-value-in-classical-hodgkin-lymphomas
#11
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/28373766/antioxidant-axis-nrf2-keap1-are-in-inhibition-of-alcoholic-liver-fibrosis-by-il-22
#12
Ya-Hui Ni, Li-Juan Huo, Ting-Ting Li
AIM: To explore the effect of interleukin (IL)-22 on in vitro model of alcoholic liver fibrosis hepatic stellate cells (HSCs), and whether this is related to regulation of Nrf2-keap1-ARE. METHODS: HSC-T6 cells were incubated with 25, 50, 100, 200 and 400 μmol/L acetaldehyde. After 24 and 48 h, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect proliferation of HSCs to choose the best concentration and action time. We used the optimal concentration of acetaldehyde (200 μmol/L) to stimulate HSCs for 24 h, and treated the cells with a final concentration of 10, 20 or 50 ng/mL IL-22...
March 21, 2017: World Journal of Gastroenterology: WJG
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
#13
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/28371750/cysteine-persulfides-and-polysulfides-produced-by-exchange-reactions-with-h2s-protect-sh-sy5y-cells-from-methylglyoxal-induced-toxicity-through-nrf2-activation
#14
Shin Koike, Shoichi Nishimoto, Yuki Ogasawara
Many physiological functions of hydrogen sulfide (H2S) have been reported in mammalian cells over the last 20 years. These physiological effects have been ascertained through in vitro treatment of cells with Na2S or NaHS, both of which are precursors of H2S. Since H2S exists as HS(-) in a neutral solution, a disulfide compound such as cystine could react with HS(-) in culture medium as well as in the cell. This study demonstrated that after the addition of Na2S solution into culture medium, HS(-) was transiently generated and disappeared immediately through the reaction between HS(-) and cystine to form cysteine persulfides and polysulfides in the culture medium (bound sulfur mixture: BS-Mix)...
March 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28371616/salvianolic-acid-a-protects-retinal-pigment-epithelium-from-ox-ldl-induced-inflammation-in-an-age-related-macular-degeneration-model
#15
Ke Mao, Wanting Shu, Qinghua Qiu, Qing Gu, Xingwei Wu
BACKGROUND: Salvianolic acid A (Sal A), an active monomer of Salvia miltiorrhiza, is a phenolic carboxylic acid derivative. The present study was performed to investigate the underlying mechanism of the anti-inflammation effect of Sal A, especially focusing on mTOR-KEAP1-Nrf2 and P2X7R-PKR-NLRP3 signaling pathways. METHODS: SD mice were divided into four groups: PBS, oxidized-low density lipoprotein (ox-LDL, 3 mg/kg), and ox-LDL (3 mg/kg) + Sal A (5 mg/kg) and + Sal A (10 mg/ml) groups...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28359760/effect-of-p62-sqstm1-polyubiquitination-on-its-autophagic-adaptor-function-and-cellular-survival-under-oxidative-stress-induced-by-arsenite
#16
Hyuna Lee, Mi-Nam Kim, Kwon-Yul Ryu
Oxidative stress induced by arsenite [As(III)] affects protein folding and results in increased levels of misfolded proteins or protein aggregates. Accumulation of misfolded protein aggregates may act as a cue signal for the oligomerization of the autophagic adaptor protein p62, which facilitates recognition of misfolded protein aggregates that are polyubiquitinated with K63 linkages. However, as the autophagic flux is impaired under exposure to As(III), p62 oligomers cannot be cleared by autophagy and accumulate as aggregates with Keap1...
March 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28343084/role-of-pterostilbene-in-attenuating-immune-mediated-devastation-of-pancreatic-beta-cells-via-nrf2-signaling-cascade
#17
Dornadula Sireesh, Munuswamy-Ramanujam Ganesh, Umapathy Dhamodharan, Murugesan Sakthivadivel, Srinivasan Sivasubramanian, Palani Gunasekaran, Kunka Mohanram Ramkumar
Nrf2 (nuclear factor erythroid 2-related factor-2) is a transcription factor that regulates oxidative/xenobiotic stress response and also suppress inflammation. Nrf2 signaling is associated with an increased susceptibility to various kinds of stress. Nrf2 has been shown as a promising therapeutic target in various human diseases including diabetes. Our earlier studies showed Pterostilbene (PTS) as a potent Nrf2 activator, and it protects the pancreatic β-cells against oxidative stress. In this study, we investigated PTS confer protection against cytokine-induced β-cell apoptosis and its role on insulin secretion in streptozotocin (STZ)-induced diabetic mice...
March 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28336552/prospective-comprehensive-molecular-characterization-of-lung-adenocarcinomas-for-efficient-patient-matching-to-approved-and-emerging-therapies
#18
Emmet J Jordan, Hyunjae R Kim, Maria E Arcila, David A Barron, Debyani Chakravarty, Jianjiong Gao, Matthew T Chang, Andy Ni, Ritika Kundra, Philip Jonsson, Gowtham Jayakumaran, Sizhi P Gao, Hannah C Johnsen, Aphrothiti J Hanrahan, Ahmet Zehir, Natasha Rekhtman, Michelle S Ginsberg, Bob T Li, Helena Yu, Paul K Paik, Alexander Drilon, Matthew D Hellmann, Dalicia N Reales, Ryma Benayed, Valerie W Rusch, Mark G Kris, Jamie E Chaft, José Baselga, Barry S Taylor, Nikolaus Schultz, Charles M Rudin, David M Hyman, Michael F Berger, David B Solit, Marc Ladanyi, Gregory J Riely
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies...
March 23, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28333129/protection-against-oxidative-stress-mediated-by-the-nrf2-keap1-axis-is-impaired-in-primary-biliary-cholangitis
#19
Urszula Wasik, Małgorzata Milkiewicz, Agnieszka Kempinska-Podhorodecka, Piotr Milkiewicz
In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315327/discovery-of-a-kelch-like-ech-associated-protein-1-inhibitory-tetrapeptide-and-its-structural-characterization
#20
Satoshi Sogabe, Kotaro Sakamoto, Yusuke Kamada, Akito Kadotani, Yasunori Fukuda, Jun-Ichi Sakamoto
Keap1 constitutively binds to the transcription factor Nrf2 to promote its degradation, resulting in negative modulation of genes involved in cellular protection against oxidative stress. Keap1 is increasingly recognized as an attractive target for treating diseases involving oxidative stress, including cancer, atherosclerosis, diabetes, arthritis, and neurodegeneration. We used phage-display peptide screening to identify a tetrapeptide showing moderate binding affinity, which inhibits the interaction between Nrf2 and Keap1...
March 14, 2017: Biochemical and Biophysical Research Communications
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