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https://www.readbyqxmd.com/read/28107678/nobiletin-and-its-colonic-metabolites-suppress-colitis-associated-colon-carcinogenesis-by-down-regulating-inos-inducing-antioxidative-enzymes-and-arresting-cell-cycle-progression
#1
Xian Wu, Mingyue Song, Zili Gao, Yue Sun, Minqi Wang, Fang Li, Jinkai Zheng, Hang Xiao
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice...
January 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28086803/compendium-of-tcdd-mediated-transcriptomic-response-datasets-in-mammalian-model-systems
#2
Stephenie D Prokopec, Kathleen E Houlahan, Ren X Sun, John D Watson, Cindy Q Yao, Jamie Lee, Christine P'ng, Renee Pang, Alexander H Wu, Lauren C Chong, Ashley B Smith, Nicholas J Harding, Ivy D Moffat, Jere Lindén, Sanna Lensu, Allan B Okey, Raimo Pohjanvirta, Paul C Boutros
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28068647/berberine-an-isoquinoline-alkaloid-suppresses-txnip-mediated-nlrp3-inflammasome-activation-in-msu-crystal-stimulated-raw-264-7-macrophages-through-the-upregulation-of-nrf2-transcription-factor-and-alleviates-msu-crystal-induced-inflammation-in-rats
#3
Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264...
January 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28065220/effects-of-lianhua-qingwen-on-pulmonary-oxidative-lesions-induced-by-fine-particulates-pm2-5-in-rats
#4
Ping Fen, Li Zhen-Sheng, Zhang Feng-Rui, Li De-Xin, Han Shu-Zhi
Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively...
November 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28028389/short-term-exposure-to-50-hz-electromagnetic-field-and-alterations-in-nqo1-and-nqo2-expression-in-mcf-7-cells
#5
Hamideh Mahmoudinasab, Mostafa Saadat
AIM: Extremely low-frequency electromagnetic fields (ELF-EMFs) have some genotoxic effects and it may alter the mRNA levels of antioxidant genes. The NAD(P)H: quinone oxidoreductase-1 (NQO1) and NQO2 are ubiquitously expressed. Considering that there is no published data on the effect(s) of ELF-EMF (50-Hz) exposure and expression levels of NQO1 and NQO2 in the human MCF-7 cells, the present study was carried out. METHODS: The ELF-EMF (0.25 and 0.50 mT) exposure patterns were: 5 min field-on/5 min filed-off, 15 min field-on/15 min field-off, and 30 min field-on continuously...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28025122/protective-effect-of-rutaecarpine-against-t-bhp-induced-hepatotoxicity-by-upregulating-antioxidant-enzymes-via-the-camkii-akt-and-nrf2-are-pathways
#6
Sun Woo Jin, Yong Pil Hwang, Chul Yung Choi, Hyung Gyun Kim, Se Jong Kim, Yongan Kim, Young Chul Chung, Kyung Jin Lee, Tae Cheon Jeong, Hye Gwang Jeong
Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of Evodia rutaecarpa, has been shown to have cytoprotective potential, but the molecular mechanism underlying this activity remains unclear. Our study was designed to investigate the cytoprotective effect of rutaecarpine against tert-butyl hydroperoxide (t-BHP) and to elucidate its action mechanism of action of rutaecarpine in a cultured HepG2 cell line and in mouse liver. Rutaecarpine decreased t-BHP-induced reactive oxygen species (ROS) production, cytotoxicity, and apoptosis in HepG2 cells...
December 23, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28012970/isoliquiritigenin-inhibits-tnf-%C3%AE-induced-release-of-high-mobility-group-box-1-through-activation-of-hdac-in-human-intestinal-epithelial-ht-29-cells
#7
Jin-Hua Chi, Geom Seog Seo, Jae Hee Cheon, Sung Hee Lee
The suppression of pro-inflammatory cytokine-induced inflammation responses is an attractive pharmacological target for the development of therapeutic strategies for inflammatory bowel disease (IBD). In the present study, we evaluated the anti-inflammatory properties of flavonoid isoliquiritigenin (ISL) in intestinal epithelial cells and determined its mechanism of action. ISL suppressed the expression of inflammatory molecules, including IL-8, IL-1β and COX-2, in TNF-α-stimulated HT-29 cells. Moreover, ISL induced activation of Nrf2 and expression of its target genes, such as HO-1 and NQO1...
December 21, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28012535/peanut-sprout-extract-attenuates-cisplatin-induced-ototoxicity-by-induction-of-the-akt-nrf2-mediated-redox-pathway
#8
Cha Kyung Youn, Eu-Ri Jo, Ju-Hwan Sim, Sung Il Cho
OBJECTIVE: Cisplatin is commonly used to treat solid tumors. However, permanent hearing loss is a major side effect of cisplatin chemotherapy and often results in dose reduction of the cisplatin chemotherapy. Peanut sprouts show cytoprotective properties owing to their antioxidant activities. This study was designed to investigate the effect of peanut sprout extract (PSE) on cisplatin-induced ototoxicity in an auditory cell line, HEI-OC1 cells. METHODS: Cells were exposed to cisplatin for 24 h, with or without pre-treatment with PSE, cell viability was examined using the MTT assay...
January 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28006669/alkynyloxy-derivatives-of-5-8-quinolinedione-synthesis-in%C3%A2-vitro-cytotoxicity-studies-and-computational-molecular-modeling-with-nad-p-h-quinone-oxidoreductase-1
#9
Monika Kadela-Tomanek, Maria Jastrzębska, Bartosz Pawełczak, Ewa Bębenek, Elwira Chrobak, Małgorzata Latocha, Maria Książek, Joachim Kusz, Stanisław Boryczka
The natural 7-amino-5,8-quinolinodione antibiotics were the substrate for the NQO1 protein. The structure-activity relationship showed that the 5,8-quinolinedione moiety was responsible for the interaction with the enzyme. In our research, we presented the synthesis, cytotoxic activity and theoretical study of a 5,8-quinolinedione compound as a potential inhibitor of the NQO1 enzyme. Mono and disubstituted alkynyloxy derivatives of the 5,8-quinolinedione were synthesized and characterized by (1)H, (13)C NMR, IR and HR-MS spectra...
December 15, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28000977/silac-based-quantitative-proteomic-analysis-reveals-widespread-molecular-alterations-in-human-skin-keratinocytes-upon-chronic-arsenic-exposure
#10
Sartaj Ahmad Mir, Sneha M Pinto, Somnath Paul, Remya Raja, Vishalakshi Nanjappa, Nazia Syed, Jayshree Advani, Santosh Renuse, Nandini A Sahasrabuddhe, T S Keshava Prasad, Ashok K Giri, Harsha Gowda, Aditi Chatterjee
Chronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epidemiological studies suggest the association of skin cancer upon arsenic exposure, however, the mechanism of arsenic-induced carcinogenesis is not completely understood...
October 19, 2016: Proteomics
https://www.readbyqxmd.com/read/28000844/cytoprotective-effects-of-esculetin-against-oxidative-stress-are-associated-with-the-upregulation-of-nrf2-mediated-nqo1-expression-via-the-activation-of-the-erk-pathway
#11
Min Ho Han, Cheol Park, Dae-Sung Lee, Su-Hyun Hong, Il-Whan Choi, Gi-Young Kim, Sung Hyun Choi, Jung-Hyun Shim, Jung-Il Chae, Young Hyun Yoo, Yung Hyun Choi
Esculetin, a coumarin derivative isolated from a variety of medicinal herbs, has been reported to possess multiple therapeutic and pharmacological actions. Although several studies have demonstrated the antioxidant activity of esculetin, its mechanisms of action have not been clearly established. The aim of this study was to evaluate the effects of esculetin against hydrogen peroxide (H2O2)‑induced oxidative stress in C2C12 myoblasts and to investigate the mechanisms involved in this process. Our data indicated that esculetin preconditioning significantly attenuated H2O2‑induced growth inhibition and DNA damage and the apoptosis of C2C12 cells by suppressing intracellular reactive oxygen species (ROS) accumulation...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27993870/possible-implication-of-gstp1-and-nqo1-polymorphisms-on-natalizumab-response-in-multiple-sclerosis
#12
Athanasia Alexoudi, Sophia Zachaki, Chrysa Stavropoulou, Stavroula Gavrili, Chara Spiliopoulou, Stavroula Papadodima, Clementine E Karageorgiou, Constantina Sambani
Oxidative stress plays a pivotal role in the pathogenesis of multiple sclerosis (MS). Inactivating polymorphism of genes encoding detoxification enzymes, such as NQO1 and GSTP1 could influence susceptibility to MS. The monoclonal antibody natalizumab is an effective treatment in MS. Natalizumab's efficacy in MS patients with regard to NQO1 and GSTP1 genetic polymorphisms is investigated. 130 patients with definite MS according to the Mc Donald's criteria treated monthly with natalizumab were included in the study...
December 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27986568/distinct-responses-of-compartmentalized-glutathione-redox-potentials-to-pharmacologic-quinones-targeting-nqo1
#13
Vladimir L Kolossov, Nagendraprabhu Ponnuraj, Jessica N Beaudoin, Matthew T Leslie, Paul J Kenis, H Rex Gaskins
Deoxynyboquinone (DNQ), a potent novel quinone-based antineoplastic agent, selectively kills solid cancers with overexpressed cytosolic NAD(P)H:quinone oxidoreductase-1 (NQO1) via excessive ROS production. A genetically encoded redox-sensitive probe was used to monitor intraorganellar glutathione redox potentials (EGSH) as a direct indicator of cellular oxidative stress following chemotherapeutic administration. Beta-lapachone (β-lap) and DNQ-induced spatiotemporal redox responses were monitored in human lung A549 and pancreatic MIA-PaCa-2 adenocarcinoma cells incubated with or without dicumarol and ES936, potent NQO1 inhibitors...
December 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27977895/a-soluble-form-of-psgl-1-requires-nrf2-signaling-to-protect-liver-transplant-endothelial-cells-against-ischemia-reperfusion-injury
#14
Cheng Zhang, Yu Zhang, Yuanxing Liu, Yuan Liu, Shoichi Kageyama, Xiu-da Shen, Feng Gao, Shusen Zheng, Ronald W Busuttil, Gray D Shaw, Haofeng Ji, Jerzy W Kupiec-Weglinski
Liver endothelial cell (LEC) damage is essential in the pathogenesis of ischemia-reperfusion injury (IRI) in transplant recipients. We analyzed the mechanism of LEC resistance against IRI by using a novel recombinant soluble form of PSGL-1 (Tandem P-Selectin Glycoprotein Ligand-Immunoglobulin; TSGL-Ig) in a mouse model of hepatic cold preservation (4°C in UW for 20h) and syngeneic orthotopic liver transplantation (OLT). Unlike in controls, TSGL-Ig protected OLT against IR-stress, evidenced by depressed sALT levels, well-preserved hepatic architecture, and improved survival (42% vs...
December 15, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27975234/pharmacokinetics-and-derivation-of-an-anticancer-dosing-regimen-for-the-novel-anti-cancer-agent-isobutyl-deoxynyboquinone-ib-dnq-a-nqo1-bioactivatable-molecule-in-the-domestic-felid-species
#15
Alycen P Lundberg, Joshua M Francis, Malgorzata Pajak, Elizabeth I Parkinson, Kathryn L Wycislo, Thomas J Rosol, Megan E Brown, Cheryl A London, Levent Dirikolu, Paul J Hergenrother, Timothy M Fan
Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase (NQO1), an enzyme overexpressed in many solid tumors. Following activation by NQO1, IB-DNQ participates in a catalytic futile reduction/reoxidation cycle with consequent toxic reactive oxygen species generation within the tumor microenvironment. To elucidate the potential of IB-DNQ to serve as a novel anticancer agent, in vitro studies coupled with in vivo pharmacokinetic and toxicologic investigations in the domestic felid species were conducted to investigate the tractability of IB-DNQ as a translationally applicable anticancer agent...
December 14, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27973423/regressive-effect-of-myricetin-on-hepatic-steatosis-in-mice-fed-a-high-fat-diet
#16
Shu-Fang Xia, Guo-Wei Le, Peng Wang, Yu-Yu Qiu, Yu-Yu Jiang, Xue Tang
Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities...
December 11, 2016: Nutrients
https://www.readbyqxmd.com/read/27966538/nqo1-inhibits-proteasome-mediated-degradation-of-hif-1%C3%AE
#17
Eun-Taex Oh, Jung-Whan Kim, Joon Mee Kim, Soo Jung Kim, Jae-Seon Lee, Soon-Sun Hong, Justin Goodwin, Robin J Ruthenborg, Myung Gu Jung, Hae-June Lee, Chul-Ho Lee, Eun Sung Park, Chulhee Kim, Heon Joo Park
Overexpression of NQO1 is associated with poor prognosis in human cancers including breast, colon, cervix, lung and pancreas. Yet, the molecular mechanisms underlying the pro-tumorigenic capacities of NQO1 have not been fully elucidated. Here we show a previously undescribed function for NQO1 in stabilizing HIF-1α, a master transcription factor of oxygen homeostasis that has been implicated in the survival, proliferation and malignant progression of cancers. We demonstrate that NQO1 directly binds to the oxygen-dependent domain of HIF-1α and inhibits the proteasome-mediated degradation of HIF-1α by preventing PHDs from interacting with HIF-1α...
December 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27960087/leveraging-an-nqo1-bioactivatable-drug-for-tumor-selective-use-of-poly-adp-ribose-polymerase-inhibitors
#18
Xiumei Huang, Edward A Motea, Zachary R Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A Kilgore, Molly A Silvers, Praveen L Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S Williams, John D Minna, Muhammad Beg, David E Gerber, Erik A Bey, David A Boothman
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1(+) cancers, such as non-small-cell lung, pancreatic, and breast cancers, cell death mechanism switches from PARP1 hyperactivation-mediated programmed necrosis with β-lapachone monotherapy to synergistic tumor-selective, caspase-dependent apoptosis with PARP inhibitors and β-lapachone...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27939991/protective-effect-of-3h-1-2-dithiole-3-thione-on-cellular-model-of-alzheimer-s-disease-involves-nrf2-are-signaling-pathway
#19
Lan Wang, Min Wang, Jing Hu, Wei Shen, Junjie Hu, Yi Yao, Xifeng Wang, Curimbacus M Afzal, Rong Ma, Gang Li
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms. Our assays demonstrated that D3T was able to attenuate reactive oxygen species generation, increase MMP level as well as decrease MDA content...
December 8, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27929184/a-comparison-of-rs4-type-resistant-starch-to-rs2-type-resistant-starch-in-suppressing-oxidative-stress-in-high-fat-diet-induced-obese-rats
#20
Xu Si, Zhongkai Zhou, Padraig Strappe, Chris Blanchard
The anti-obesity effects of two types of resistant starch (RS) in high-fat-diet-induced obese rats were investigated. The serum triglycerides, total cholesterol and malondialdehyde concentrations were significantly reduced, and the total antioxidant capacity, superoxide dismutase levels and glutathione peroxidase activity were increased by RS2 and RS4 consumption compared to the obesity group. A significant reduction in the serum glucose level and elevations in hepatic lipid metabolic enzyme activities were observed only for RS4 administration...
December 8, 2016: Food & Function
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