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NAD AND NQO1

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https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#1
Mario Pink, Nisha Verma, Anna Zerries, Simone Schmitz-Spanke
A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterise the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 µM (environmentally relevant) to 80 µM by utilising toxicological and metabolomic approaches...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#2
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28905938/triptolide-induces-sertoli-cell-apoptosis-in-mice-via-ros-jnk-dependent-activation-of-the-mitochondrial-pathway-and-inhibition-of-nrf2-mediated-antioxidant-response
#3
Yu Wang, Su-Han Guo, Xue-Jun Shang, Li-Sha Yu, Jian-Wei Zhu, Ang Zhao, Yan-Fen Zhou, Guo-Hua An, Qi Zhang, Bo Ma
Triptolide (TP), an oxygenated diterpene, has a variety of beneficial pharmacodynamic activities but its clinical applications are restricted due to severe testicular injury. This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28883796/functions-of-nqo1-in-cellular-protection-and-coq10-metabolism-and-its-potential-role-as-a-redox-sensitive-molecular-switch
#4
REVIEW
David Ross, David Siegel
NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28881715/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#5
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868496/pancreatic-mitochondrial-complex-i-exhibits-aberrant-hyperactivity-in-diabetes
#6
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD(+) redox balance is heavily perturbed in diabetes, and the NADH/NAD(+) redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD(+) regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD(+) redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28865326/hydrogen-sulfide-attenuates-calcification-of-vascular-smooth-muscle-cells-via-keap1-nrf2-nqo1-activation
#7
Parisa Aghagolzadeh, Ramin Radpour, Matthias Bachtler, Harry van Goor, Edward R Smith, Adam Lister, Alex Odermatt, Martin Feelisch, Andreas Pasch
BACKGROUND AND AIMS: Vascular calcification is a common health problem related to oxidative stress, inflammation, and circulating calciprotein particles (CPP). Hydrogen sulfide is an endogenous signaling molecule with antioxidant properties and potential for drug development targeting redox signaling. Yet, its molecular mechanisms of action in vascular smooth muscle cell (VSMC) calcification have not been delineated. We therefore sought to identify key pathways involved in the calcification-inhibitory properties of sulfide employing our recently developed CPP-induced VSMC calcification model...
August 19, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28863281/aging-related-decline-in-the-induction-of-nrf2-regulated-antioxidant-genes-in-human-bronchial-epithelial-cells
#8
Lulu Zhou, Hongqiao Zhang, Kelvin J A Davies, Henry Jay Forman
Evidence from animal studies suggests that stress-induced increases in Nrf2-regulated antioxidant gene expression, a critical mechanism of cellular protection, declines with aging. This study examined whether this also occurs in humans. We measured the basal and inducible levels of Nrf2-regulated antioxidant genes in human bronchial epithelial (HBE) cells from subjects of young adult (21-29 years) and older (60-69 years) non-smokers, and explored factors affecting expresion. The basal expression of three representative Nrf2-regulated genes, the catalytic and modulator subunits of glutamate cysteine ligase (GCLC and GCLM, respectively), and NAD(P)H quinone oxidoreductase 1 (NQO1), was higher in cells from the older donors compared with cells from the young adult donors...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28846887/attenuation-of-cyclosporine-a-induced-nephrotoxicity-by-schisandrin-b-through-suppression-of-oxidative-stress-apoptosis-and-autophagy
#9
Qiao Lai, Zhengzhong Luo, Chunying Wu, Sisi Lai, Hanmei Wei, Tongming Li, Qing Wang, Yang Yu
Cyclosporine A (CsA) is a potent immunosuppressive agent whose clinical usage is limited by nephrotoxicity. Schisandrin B (SchB), isolated from the fruit of Schisandra chinensis, is a natural compound with multiple pharmacological activities that has been shown to attenuate organ injury caused by CsA. Hence, the primary objective of the current study was to evaluate whether SchB has a cytoprotective effect on CsA-induced nephrotoxicity in human proximal tubular epithelial cell line (HK-2). This study demonstrated that pre-incubation of HK-2 cells with 2...
August 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28833669/a-tumor-specific-cascade-amplification-drug-release-nanoparticle-for-overcoming-multidrug-resistance-in-cancers
#10
Mingzhou Ye, Yuxin Han, Jianbin Tang, Ying Piao, Xiangrui Liu, Zhuxian Zhou, Jianqing Gao, Jianghong Rao, Youqing Shen
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β-lapachone and a reactive-oxygen-species (ROS)-responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β-lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects...
August 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28816586/oxidative-stress-in-the-visceral-fat-is-elevated-in-postmenopausal-women-with-gynecologic-cancer
#11
Megumi Narumi, Kazuhiro Takahashi, Hizuru Yamatani, Manabu Seino, Keiko Yamanouchi, Tsuyoshi Ohta, Toshifumi Takahashi, Hirohisa Kurachi, Satoru Nagase
OBJECTIVES: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes. MATERIALS AND METHODS: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive oxygen species (ROS) production that was induced by hydrogen peroxide (H2O2) in 3T3-L1 adipocytes...
August 17, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28812892/designer-extracts-as-tools-to-balance-estrogenic-and-chemopreventive-activities-of-botanicals-for-women-s-health
#12
Birgit M Dietz, Shao-Nong Chen, René F Ramos Alvarenga, Huali Dong, Dejan Nikolić, Martin Biendl, Richard B van Breemen, Judy L Bolton, Guido F Pauli
Botanical dietary supplements contain multiple bioactive compounds that target numerous biological pathways. The lack of uniform standardization requirements is one reason that inconsistent clinical effects are reported frequently. The multifaceted biological interactions of active principles can be disentangled by a coupled pharmacological/phytochemical approach using specialized ("knock-out") extracts. This is demonstrated for hops, a botanical for menopausal symptom management. Employing targeted, adsorbent-free countercurrent separation, Humulus lupulus extracts were designed for pre- and postmenopausal women by containing various amounts of the phytoestrogen 8-prenylnaringenin (8-PN) and the chemopreventive constituent xanthohumol (XH)...
August 16, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28798861/overexpression-of-brg1-alleviates-hepatic-ischemia-reperfusion-induced-acute-lung-injury-through-antioxidative-stress-effects
#13
Mian Ge, Chaojin Chen, Weifeng Yao, Shaoli Zhou, Fei Huang, Jun Cai, Ziqing Hei
AIM: To investigate whether overexpression of Brahma-related gene-1 (Brg1) can alleviate lung injury induced by hepatic ischemia/reperfusion (HIR) and its precise mechanism. METHODS: Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice and wild-type (WT) C57BL/6 mice underwent HIR. Lung histology, oxidative injury markers, and antioxidant enzyme concentrations in the lung were assessed. The protein expression levels of Brg1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the lung were analyzed by Western blotting...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28792522/biochemical-characterization-and-anti-inflammatory-properties-of-an-isothiocyanate-enriched-moringa-moringa-oleifera-seed-extract
#14
Asha Jaja-Chimedza, Brittany L Graf, Charlotte Simmler, Youjin Kim, Peter Kuhn, Guido F Pauli, Ilya Raskin
Moringa oleifera Lam. is a tropical plant, used for centuries as food and traditional medicine. The aim of this study was to develop, validate and biochemically characterize an isothiocyanate-enriched moringa seed extract (MSE), and to compare the anti-inflammatory effects of MSE-containing moringa isothiocyanate-1 (MIC-1) with a curcuminoid-enriched turmeric extract (CTE), and a material further enriched in its primary phytochemical, curcumin (curcumin-enriched material; CEM). MSE was prepared by incubating ground moringa seeds with water to allow myrosinase-catalyzed enzymatic formation of bioactive MIC-1, the predominant isothiocyanate in moringa seeds...
2017: PloS One
https://www.readbyqxmd.com/read/28783600/selenium-antagonizes-cadmium-induced-apoptosis-in-chicken-spleen-but-not-involving-nrf2-regulated-antioxidant-response
#15
Menghao Chen, Xiaojing Li, Ruifeng Fan, Changyu Cao, Haidong Yao, Shiwen Xu
The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl2, 150mg/kg) and sodium selenite (Na2SeO3, 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days...
August 4, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28780322/reduction-of-oxidative-damages-induced-by-titanium-dioxide-nanoparticles-correlates-with-induction-of-the-nrf2-pathway-by-gspe-supplementation-in-mice
#16
Linpeng Niu, Mengjiao Shao, Yuan Liu, Jinfeng Hu, Ruofan Li, Heran Xie, Lixiao Zhou, Lei Shi, Rong Zhang, Yujie Niu
Titanium dioxide nanoparticles (TiO2 NPs) are widely used to additives in cosmetics, pharmaceuticals, paints and foods. Recent studies have demonstrated that TiO2 NPs increased the risk of cancer and the mechanism might relate with oxidative stress. Grape seed procyanidin extract (GSPE) is a natural compound which has been demonstrated to possess a wide array of pharmacological and biochemical actions, including anti-inflammatory, anti-carcinogenic, and antioxidant properties. Our data show that GSPE prevents the changes of histopathology and biomarkers in heart, liver and kidney that occur in mice exposed to TiO2 NPs...
August 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28761325/taxifolin-protects-rpe-cells-against-oxidative-stress-induced-apoptosis
#17
Xiaobin Xie, Jun Feng, Zefeng Kang, Shoukang Zhang, Lixia Zhang, Yan Zhang, Xuefei Li, Youzhi Tang
PURPOSE: Oxidative stress-induced damage to RPE cells has been suggested to be an important factor in the pathogenesis of age-related macular degeneration. Taxifolin, a flavonol, has been shown to exhibit significant antioxidant properties. The purpose of this study was to investigate the potential protective effects of taxifolin on RPE cells cultured under oxidative stress conditions and to elucidate the underlying mechanisms. METHODS: Human RPE (ARPE-19) cells were treated with different concentrations of taxifolin and 0...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28748640/expression-of-nad-p-h-quinone-dehydrogenase-1-nqo1-is-increased-in-the-endometrium-of-women-with-endometrial-cancer-and-women-with-polycystic-ovary-syndrome
#18
William Atiomo, Mohamad Nasir Shafiee, Caroline Chapman, Veronika M Metzler, Jad Abouzeid, Ayşe Latif, Amy Chadwick, Sarah Kitson, Vanitha N Sivalingam, Ian J Stratford, Catrin S Rutland, Jenny L Persson, Niels Ødum, Pablo Fuentes-Utrillia, Jennie N Jeyapalan, David M Heery, Emma J Crosbie, Nigel P Mongan
OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). AIM: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC...
July 27, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28736552/asiatic-acid-exhibits-anti-inflammatory-and-antioxidant-activities-against-lipopolysaccharide-and-d-galactosamine-induced-fulminant-hepatic-failure
#19
Hongming Lv, Zhimin Qi, Sisi Wang, Haihua Feng, Xuming Deng, Xinxin Ci
Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28733231/tussilagonone-induced-nrf2-pathway-activation-protects-hepg2-cells-from-oxidative-injury
#20
Kyung-Mi Lee, Tae Yeon Kwon, Unwoo Kang, Eun Kyoung Seo, Ji Ho Yun, Chu Won Nho, Yeong Shik Kim
Tussilagonone is a compound derived from the medicinal plant Tussilago farfara L., which is used as a traditional medicine for respiratory diseases, including asthma and pneumonia. Recent reports suggest that tussilagonone exhibits anti-inflammatory effects; however, the scope of protective functions has not been elucidated yet. In this study, we demonstrate that tussilagonone enhances cellular detoxification by increasing quinone reductase activity in Hepa1c1c7 cells. In addition, tussilagonone decreased tert-butyl hydroperoxide(t-BHP)-induced ROS production and cell death, suggesting that it also acts as a potent antioxidant...
July 18, 2017: Food and Chemical Toxicology
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