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NAD+ AND NQO1

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https://www.readbyqxmd.com/read/28203294/correlation-between-nad-p-h-quinone-oxidoreductase-1-c609t-polymorphism-and-increased-risk-of-esophageal-cancer-evidence-from-a-meta-analysis
#1
Jingfang Diao, Jie Bao, Jianxin Peng, Jiaqiang Mo, Qing Ye, Junming He
NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28192119/leflunomide-induces-nad-p-h-quinone-dehydrogenase-1-enzyme-via-the-aryl-hydrocarbon-receptor-in-neonatal-mice
#2
Amrit Kumar Shrestha, Ananddeep Patel, Renuka T Menon, Weiwu Jiang, Lihua Wang, Bhagavatula Moorthy, Binoy Shivanna
Aryl hydrocarbon receptor (AhR) has been increasingly recognized to play a crucial role in normal physiological homeostasis. Additionally, disrupted AhR signaling leads to several pathological states in the lung and liver. AhR activation transcriptionally induces detoxifying enzymes such as cytochrome P450 (CYP) 1A and NAD(P)H quinone dehydrogenase 1 (NQO1). The toxicity profiles of the classical AhR ligands such as 3-methylcholanthrene and dioxins limit their use as a therapeutic agent in humans. Hence, there is a need to identify nontoxic AhR ligands to develop AhR as a clinically relevant druggable target...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28191864/overexpression-of-nad-p-h-quinone-oxidoreductase-1-inhibits-hepatocellular-carcinoma-cell-proliferation-and-induced-apoptosis-by-activating-ampk-pgc-1%C3%AE-pathway
#3
Xin Zhang, Kun Han, Dong-Hong Yuan, Cun-Ying Meng
Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis...
February 13, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#4
Hongming Lv, Qinmei Liu, Junfeng Zhou, Guangyun Tan, Xuming Deng, Xinxin Ci
Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28159760/nad-p-h-quinone-oxidoreductase-1-nqo1-competes-with-20s-proteasome-for-binding-with-c-ebp%C3%AE-leading-to-its-stabilization-and-protection-against-radiation-induced-myeloproliferative-disease
#5
https://www.readbyqxmd.com/read/28108387/inhibition-of-monoamine-oxidase-b-by-selegiline-reduces-cigarette-smoke-induced-oxidative-stress-and-inflammation-in-airway-epithelial-cells
#6
Yuting Cui, Kenneth W K Liu, Yingmin Liang, Mary S M Ip, Judith C W Mak
Chronic obstructive pulmonary disease (COPD) is caused by the build-up of oxidative stress-induced damages due to cigarette smoking, but how monoamine oxidase (MAO)-B signaling is involved remains unclear. This study aims to establish the involvement of MAO-B signaling pathways in cigarette smoke medium (CSM)-induced oxidative stress and inflammation in human airway epithelial cells (AECs). CSM treatment increased MAO-B activity, ROS levels and IL-8 release in AECs. Pretreatment with MAO-B selective inhibitor selegiline reversed the CSM-induced changes in MAO-B activity, ROS levels and IL-8 release in a dose-dependent manner...
February 15, 2017: Toxicology Letters
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
#7
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
#8
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...
February 2017: Food and Chemical Toxicology
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/27986568/distinct-responses-of-compartmentalized-glutathione-redox-potentials-to-pharmacologic-quinones-targeting-nqo1
#12
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...
January 29, 2017: Biochemical and Biophysical Research Communications
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
#13
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
#14
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/27960087/leveraging-an-nqo1-bioactivatable-drug-for-tumor-selective-use-of-poly-adp-ribose-polymerase-inhibitors
#15
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/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#16
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27912883/miltirone-protects-human-ea-hy926-endothelial-cells-from-oxidized-low-density-lipoprotein-derived-oxidative-stress-via-a-heme-oxygenase-1-and-mapk-nrf2-dependent-pathway
#17
Liu Zhang, Hui Zhang, Xueyan Li, Bingjie Jia, Yuyu Yang, Ping Zhou, Ping Li, Jun Chen
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is an underlying cause of endothelial dysfunction, which is an early event in the pathogenesis of atherosclerosis. In our previous study, we established an ARE-driven luciferase reporter system and screened out several potential Nrf2 activators from Salvia miltiorrhiza Bunge. PURPOSE: Since miltirone showed the most potent ARE-driven luciferase activity, the aim of this study was to test the protective role of miltirone against oxidative stress in endothelial cell and to investigate the underlying mechanistic signaling pathways...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27903425/activation-of-akt-and-jnk-nrf2-nqo1-pathway-contributes-to-the-protective-effect-of-coptisine-against-aaph-induced-oxidative-stress
#18
Yin-Ran Hu, Hang Ma, Zong-Yao Zou, Kai He, Yu-Bo Xiao, Yue Wang, Min Feng, Xiao-Li Ye, Xue-Gang Li
Coptisine (COP) is one of the main active constituents of Coptidis Rhizoma. Previous studies have clarified that COP possesses antioxidant activity, but its defensive effects against pathological characteristics accompanied by oxidative damage in animal models and antioxidant mechanism are still unclear. Therefore, our purpose was to confirm the antioxidant activity of COP and explore its mechanism of action. We first detected the effects of COP on intracellular reactive oxygen species (ROS), heart beating rate, lipid peroxidation and cell death in zebrafish model with AAPH-induced oxidative stress...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27888691/redox-imbalance-and-mitochondrial-abnormalities-in-the-diabetic-lung
#19
Jinzi Wu, Zhen Jin, Liang-Jun Yan
Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD(+) redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung...
November 17, 2016: Redox Biology
https://www.readbyqxmd.com/read/27884351/in%C3%A2-vivo-imaging-of-antioxidant-response-element-activity-during-liver-regeneration-after-partial-hepatectomy
#20
Patrick Hamid Alizai, Lea Bertram, Athanassios Fragoulis, Christoph J Wruck, Daniela C Kroy, Uwe Klinge, Ulf P Neumann, Maximilian Schmeding
BACKGROUND: The nuclear factor-erythroid 2-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway is important for the regulation of antioxidative stress response and detoxification. To activate the expression of its target genes, such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1), Nrf2 binds to the ARE within the promoter region of these genes. Partial hepatectomy and consecutive liver regeneration lead to oxidative stress with activation of the Nrf2-ARE pathway...
December 2016: Journal of Surgical Research
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