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NQO2

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https://www.readbyqxmd.com/read/29025057/nqo2-inhibition-relieves-reactive-oxygen-species-effects-on-mouse-oocyte-meiotic-maturation-and-embryo-development
#1
Dandan Chen, Xin Li, Xiaoyun Liu, Xiaoyu Liu, Xiuying Jiang, Juan Du, Qian Wang, Yuanjing Liang, Wei Ma
NRH: quinone oxidoreductase 2 (NQO2) is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone to hydroquinones. Herein, we assessed the protein expression, subcellular localization, and possible functions of NQO2 in mouse oocyte meiotic maturation and embryo development. Western blot analysis detected high and stable protein expression of NQO2 in mouse oocytes during meiotic progression. Immunofluorescence illustrated NQO2 distribution on nuclear membrane, chromosomes, and meiotic spindles...
October 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28346733/the-ontogeny-and-population-variability-of-human-hepatic-dihydronicotinamide-riboside-quinone-oxidoreductase-nqo2
#2
Zoe Riches, Yuejian Liu, Jacob M Berman, Gurinder Walia, Abby C Collier
Dihydronicotinamide riboside:quinone oxidoreductase (NQO2) is an enzyme that performs reduction reactions involved in antioxidant defense. We hypothesized that NQO2 hepatic drug clearance would develop in children over time, similar to NQO1. Using human liver cytosol (n = 117), the effects of age, sex, ethnicity, and weight on NQO2 expression and activity were probed. No significant correlations were observed. Biochemical activity of NQO2 was as high at birth as in adults (0.23 ± 0.04 nmol/min/mg protein, mean ± SEM, range 0-1...
August 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28159766/nqo1-and-nqo2-regulation-of-humoral-immunity-and-autoimmunity
#3
Karim Iskander, Jessica Li, Shuhua Han, Biao Zheng, Anil K Jaiswal
No abstract text is available yet for this article.
February 3, 2017: Journal of Biological Chemistry
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
#4
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/27692612/k-efflux-independent-nlrp3-inflammasome-activation-by-small-molecules-targeting-mitochondria
#5
Christina J Groß, Ritu Mishra, Katharina S Schneider, Guillaume Médard, Jennifer Wettmarshausen, Daniela C Dittlein, Hexin Shi, Oliver Gorka, Paul-Albert Koenig, Stephan Fromm, Giovanni Magnani, Tamara Ćiković, Lara Hartjes, Joachim Smollich, Avril A B Robertson, Matthew A Cooper, Marc Schmidt-Supprian, Michael Schuster, Kate Schroder, Petr Broz, Claudia Traidl-Hoffmann, Bruce Beutler, Bernhard Kuster, Jürgen Ruland, Sabine Schneider, Fabiana Perocchi, Olaf Groß
Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is licensed for the treatment of viral infections and cancers of the skin. Imiquimod has TLR7-independent activities that are mechanistically unexplained, including NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer cells. We investigated the mechanism of inflammasome activation by imiquimod and the related molecule CL097 and determined that K(+) efflux was dispensable for NLRP3 activation by these compounds...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27586145/association-between-polymorphisms-in-xenobiotic-detoxification-related-genes-with-prognosis-of-epithelial-ovarian-cancer
#6
Juliana Carron, Angelo Borsarelli Carvalho Brito, Ana Carolina Mourão Torelli, Cristiane Oliveira, Sophie Françoise Mauricette Derchain, Carmen Silvia Passos Lima, Gustavo Jacob Lourenço
This study aimed to evaluate whether GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G and NQO2 c.-102A>C polymorphisms, involved in xenobiotic detoxification pathways, alter outcomes of epithelial ovarian cancer (EOC) patients. DNA from 84 EOC patients diagnosed at the University of Campinas Academic Hospital from January 1995 and July 2007 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival and overall survival (OS) of EOC patients was examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox proportional hazard ratio (HR) regression analyses...
October 2016: Medical Oncology
https://www.readbyqxmd.com/read/27168101/genetic-risk-factors-for-clozapine-induced-neutropenia-and-agranulocytosis-in-a-dutch-psychiatric-population
#7
K van der Weide, H Loovers, K Pondman, J Bogers, T van der Straaten, E Langemeijer, D Cohen, J Commandeur, J van der Weide
Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0...
October 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27165481/genome-wide-analysis-of-long-noncoding-rna-lncrna-expression-in-colorectal-cancer-tissues-from-patients-with-liver-metastasis
#8
Dong Chen, Qiang Sun, Xiaofei Cheng, Lufei Zhang, Wei Song, Dongkai Zhou, Jianjiang Lin, Weilin Wang
The liver is the most frequent site of metastasis in colorectal cancer (CRC), in which long noncoding RNAs (lncRNAs) may play a crucial role. In this study, we performed a genome-wide analysis of lncRNA expression to identify novel targets for the further study of liver metastasis in CRC. Samples obtained from CRC patients were analyzed using Arraystar human 8 × 60K lncRNA/mRNA v3.0 microarrays chips to find differentially expressed lncRNAs and mRNAs. The results were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR)...
July 2016: Cancer Medicine
https://www.readbyqxmd.com/read/26854376/non-symmetrical-furan-amidines-as-novel-leads-for-the-treatment-of-cancer-and-malaria
#9
Soraya Alnabulsi, Elham Santina, Ilaria Russo, Buthaina Hussein, Manikandan Kadirvel, Amy Chadwick, Elena V Bichenkova, Richard A Bryce, Karen Nolan, Constantinos Demonacos, Ian J Stratford, Sally Freeman
NRH:quinone oxidoreductase 2 enzyme (NQO2) is a potential therapeutic target in cancer and neurodegenerative diseases, with roles in either chemoprevention or chemotherapy. Here we report the design, synthesis and evaluation of non-symmetrical furan-amidines and their analogues as novel selective NQO2 inhibitors with reduced adverse off-target effects, such as binding to DNA. A pathway for the synthesis of the non-symmetrical furan-amidines was established from the corresponding 1,4-diketones. The synthesized non-symmetrical furan-amidines and their analogues showed potent NQO2 inhibition activity with nano-molar IC50 values...
March 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26636353/binding-of-dna-intercalating-agents-to-oxidized-and-reduced-quinone-reductase-2
#10
Kevin K K Leung, Brian H Shilton
Quinone reductase 2 (NQO2) is an enzyme that might have intracellular signaling functions. NQO2 can exist in either an oxidized state or a reduced state, and binding of compounds to one or both of these states inhibits enzymatic activity and could also affect intracellular signaling. A wide range of planar aromatic compounds bind NQO2, and we have identified three DNA-intercalating agents [ethidium bromide, acridine orange (AO), and doxorubicin] as novel nanomolar inhibitors of NQO2. Ethidium and AO, which carry a positive charge in their aromatic ring systems, bound reduced NQO2 with an affinity 50-fold higher than that of oxidized NQO2, while doxorubicin bound only oxidized NQO2...
December 29, 2015: Biochemistry
https://www.readbyqxmd.com/read/26596265/down-regulation-of-antioxidant-genes-in-human-sh-sy5y-cells-after-treatment-with-morphine
#11
Khyber Saify, Iraj Saadat, Mostafa Saadat
AIMS: Morphine strongly induces reactive oxygen species (ROS). The deleterious actions of morphine can be countered by antioxidant system. In the present study, we investigated the expression levels of nine antioxidant genes in human SH-SY5Y cells treated with morphine. MAIN METHODS: The cells were treated with three final concentrations of morphine (1, 5, and 10 μmol) for four exposure times (1 h, 24 h, 72 h and 18 days). The mRNA levels were determined using quantitative real-time RCR...
January 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/26521207/structure-based-de-novo-design-molecular-docking-and-molecular-dynamics-of-primaquine-analogues-acting-as-quinone-reductase-ii-inhibitors
#12
Erika Murce, Teobaldo Ricardo Cuya-Guizado, Helmut Isaac Padilla-Chavarria, Tanos Celmar Costa França, Andre Silva Pimentel
Primaquine is a traditional antimalarial drug with low parasitic resistance and generally good acceptance at higher doses, which has been used for over 60 years in malaria treatment. However, several limitations related to its hematotoxicity have been reported. It is believed that this toxicity comes from the hydroxylation of the C-5 and C-6 positions of its 8-aminoquinoline ring before binding to the molecular target: the quinone reductase II (NQO2) human protein. In this study we propose primaquine derivatives, with substitution at position C-6 of the 8-aminoquinoline ring, planned to have better binding to NQO2, compared to primaquine, but with a reduced toxicity related to the C-5 position being possible to be oxidized...
November 2015: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/26046590/parkinsonian-toxin-induced-oxidative-stress-inhibits-basal-autophagy-in-astrocytes-via-nqo2-quinone-oxidoreductase-2-implications-for-neuroprotection
#13
Elzbieta Janda, Antonella Lascala, Cristina Carresi, Maddalena Parafati, Serafina Aprigliano, Vanessa Russo, Claudia Savoia, Elena Ziviani, Vincenzo Musolino, Federica Morani, Ciro Isidoro, Vincenzo Mollace
Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular target of neurotoxins in the brain. PQ decreased the basal levels of LC3-II and LC3-positive vesicles, and its colocalization with lysosomal markers, both in the absence and presence of chloroquine...
2015: Autophagy
https://www.readbyqxmd.com/read/25556939/biogps-navigating-biological-space-to-predict-polypharmacology-off-targeting-and-selectivity
#14
Lydia Siragusa, Simon Cross, Massimo Baroni, Laura Goracci, Gabriele Cruciani
The structural comparison of protein binding sites is increasingly important in drug design; identifying structurally similar sites can be useful for techniques such as drug repurposing, and also in a polypharmacological approach to deliberately affect multiple targets in a disease pathway, or to explain unwanted off-target effects. Once similar sites are identified, identifying local differences can aid in the design of selectivity. Such an approach moves away from the classical "one target one drug" approach and toward a wider systems biology paradigm...
March 2015: Proteins
https://www.readbyqxmd.com/read/25437045/the-endometrial-cancer-cell-lines-ishikawa-and-hec-1a-and-the-control-cell-line-hieec-differ-in-expression-of-estrogen-biosynthetic-and-metabolic-genes-and-in-androstenedione-and-estrone-sulfate-metabolism
#15
Neli Hevir-Kene, Tea Lanišnik Rižner
Estrogens have important roles in the pathogenesis of endometrial cancer. They can have carcinogenic effects through stimulation of cell proliferation or formation of DNA-damaging species. To characterize model cell lines of endometrial cancer, we determined the expression profiles of the estrogen receptors (ERs) ESR1, ESR2 and GPER, and 23 estrogen biosynthetic and metabolic genes, and investigated estrogen biosynthesis in the control HIEEC cell line and the Ishikawa and HEC-1A EC cell lines. HIEEC and Ishikawa expressed all ERs to different extents, while HEC-1A cells lacked expression of ESR1...
June 5, 2015: Chemico-biological Interactions
https://www.readbyqxmd.com/read/25379648/quinone-reductase-2-is-an-adventitious-target-of-protein-kinase-ck2-inhibitors-tbbz-tbi-and-dmat
#16
Kevin K K Leung, Brian H Shilton
Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein kinase CK2 inhibitors, 4,5,6,7-1H-tetrabromobenzimidazole (TBBz) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). TBBz and DMAT induce apoptosis in cells expressing an inhibitor-resistant CK2, suggesting that the interaction with NQO2 may mediate some of their pharmacological effects. In this study, we have fully characterized the binding of TBBz and DMAT to NQO2. Fluorescence titrations showed that TBBz and DMAT bind oxidized NQO2 in the low nanomolar range; in the case of TBBz, the affinity for NQO2 was 40-fold greater than its affinity for CK2...
January 13, 2015: Biochemistry
https://www.readbyqxmd.com/read/25313982/nqo2-is-a-reactive-oxygen-species-generating-off-target-for-acetaminophen
#17
Teemu P Miettinen, Mikael Björklund
The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity...
December 1, 2014: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/25169438/the-effect-of-resveratrol-and-its-methylthio-derivatives-on-the-nrf2-are-pathway-in-mouse-epidermis-and-hacat-keratinocytes
#18
Violetta Krajka-Kuźniak, Hanna Szaefer, Tomasz Stefański, Stanisław Sobiak, Michał Cichocki, Wanda Baer-Dubowska
Resveratrol is the most extensively studied stilbene derivative. We previously showed that methylthiostilbenes were more effective inhibitors of CYP1A1 and 1B1 activity than resveratrol. In this study, we investigated whether resveratrol and its methylthio-substituted derivatives, i.e. 3-M-4'-MTS (S2), 3,5-DM-4'-MTS (S5) and 3,4,5-TM-4'-MTS (S7) could activate Nrf2 signaling in the mouse epidermis and in human keratinocytes. Western blot analysis showed translocation of Nrf2 from the cytosol to the nucleus in both models...
September 2014: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/25130546/identification-of-one-electron-reductases-that-activate-both-the-hypoxia-prodrug-sn30000-and-diagnostic-probe-ef5
#19
Jingli Wang, Chris P Guise, Gabi U Dachs, Yen Phung, Annie Huai-Ling Hsu, Neil K Lambie, Adam V Patterson, William R Wilson
SN30000 is a second-generation benzotriazine-N-oxide hypoxia-activated prodrug scheduled for clinical trial. Previously we showed that covalent binding of the hypoxia probe EF5 predicts metabolic activation of SN30000 in a panel of cancer cell lines under anoxia, suggesting that they are activated by the same reductases. However the identity of these reductases is unknown. Here, we test whether forced expression of nine oxidoreductases with known or suspected roles in bioreductive prodrug metabolism (AKR1C3, CYB5R3, FDXR, MTRR, NDOR1, NOS2A, NQO1, NQO2 and POR) enhances oxic or anoxic reduction of SN30000 and EF5 by HCT116 cells...
October 15, 2014: Biochemical Pharmacology
https://www.readbyqxmd.com/read/25055937/pharmacogenetics-of-adjuvant-breast-cancer-treatment-with-cyclophosphamide-epirubicin-and-5-fluorouracil
#20
David Jamieson, Jo Lee, Nicola Cresti, Rosanna Jackson, Melanie Griffin, Julieanne Sludden, Mark Verrill, Alan V Boddy
PURPOSE: Most adjuvant breast cancer treatment regimens include the combination of an anthracycline (epirubicin or doxorubicin) and the alkylating agent cyclophosphamide. This study sought to investigate the influence of pharmacogenetics on the pharmacokinetics and metabolism of these agents. METHODS: Blood samples were taken from patients treated with cyclophosphamide (n = 51) and epirubicin (n = 35), with or without 5-fluorouracil (5-FU). The pharmacokinetics and metabolism of the three drugs were investigated, together with pharmacogenetic investigations for cyclophosphamide and epirubicin...
October 2014: Cancer Chemotherapy and Pharmacology
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