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NAD AND NQO1

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https://www.readbyqxmd.com/read/29144506/soluble-p-selectin-promotes-retinal-ganglion-cell-survival-through-activation-of-nrf2-signaling-after-ischemia-injury
#1
Kishan Kapupara, Yao-Tseng Wen, Rong-Kung Tsai, Shun-Ping Huang
Retinal ischemic injuries play an important role in the pathogenesis of several eye disorders. Inflammation and oxidative stress are key players in ischemic injuries. Following retinal ischemia, vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules. P-selectin stimulates leukocyte recruitment to platelet aggregates and has an important role in vascular homeostasis and inflammatory leukocyte extravasation. Soluble P-selectin can be neuroprotective through competitive binding to the receptors of endogenous P-selectin molecules...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29143802/the-inhibitory-effects-of-cobalt-protoporphyrin-ix-and-cannabinoid-2-receptor-agonists-in-type-2-diabetic-mice
#2
Christina McDonnell, Sergi Leánez, Olga Pol
The activation of the transcription factor Nrf2 inhibits neuropathy and modulates the activity of delta-opioid receptors (DOR) in type 2 diabetic mice but the impact of Nrf2/HO-1 pathway on the antinociceptive actions of cannabinoid 2 receptors (CB2R) has not been assessed. Using male mice BKS.Cg-m+/+Leprdb/J (db/db) we investigated if treatment with cobalt protoporphyrin IX (CoPP), an HO-1 inductor, inhibited mechanical allodynia, hyperglycemia and obesity associated to type 2 diabetes. The antinociceptive effects of JWH-015 and JWH-133 (CB2R agonists) administered with and without CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, have been also evaluated...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#3
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29110315/nad-p-h-quinone-oxidoreductase-1-silencing-aggravates-hormone-induced-prostatic-hyperplasia-in-mice
#4
H-T Kim, Y-J Kim, S-R Park, S-Y Ryu, J-Y Jung
NAD(P)H-quinone oxidoreductase 1 (NQO1) is a highly inducible flavoprotein known to involve in various cellular defence mechanisms. In this study, we explored whether NQO1 deletion affects hormone-induced prostatic hyperplasia. Testosterone propionate (3 mg/kg, IP) was injected into wild-type (WT) and NOQ1 knockout C57BL/6 mice (NQO1(-/-) ) for 14 consecutive days, and the samples were collected for biological and histochemical studies. The testosterone-treated NQO1(-/-) showed about 140% higher prostate weight than the testosterone-treated WT, with enhanced connective tissue and hyperplastic glands formations...
November 6, 2017: Andrologia
https://www.readbyqxmd.com/read/29108775/facilitation-of-9-10-phenanthrenequinone-elicited-neuroblastoma-cell-apoptosis-by-nad-p-h-quinone-oxidoreductase-1
#5
Toshiyuki Matsunaga, Kyoko Kamase, Hiroaki Takasawa, Yukiko Yamaji, Satoshi Endo, Ossama El-Kabbani, Akira Ikari
9,10-Phenanthrenequinone (PQ), a major quinone component in diesel exhaust particles, is considered to provoke damage of respiratory and vascular cells through highly producing reactive oxygen species (ROS), but little is known about its pathophysiological role in neuronal cell damage. In this study, we found that incubation with 1,2-naphthoquinone, 1,4-naphthoquinone and PQ, major quinone components in diesel exhausts, provokes apoptosis of human neuroblastoma cell lines. SK-N-SH cell treatment with a lethal concentration of PQ facilitated ROS production within 6 h...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29100982/thermodynamics-of-cooperative-binding-of-fad-to-human-nqo1-implications-to-understanding-cofactor-dependent-function-and-stability-of-the-flavoproteome
#6
Rafael Clavería-Gimeno, Adrian Velazquez-Campoy, Angel Luis Pey
The stability of human flavoproteins strongly depends on flavin levels, although the structural and energetic basis of this relationship is poorly understood. Here, we report an in-depth analysis on the thermodynamics of FAD binding to one of the most representative examples of such relationship, NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a dimeric enzyme that tightly binds FAD, which triggers large structural changes upon binding. A common cancer-associated polymorphism (P187S) severely compromises FAD binding...
October 31, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29066863/pharmacokinetic-and-safety-evaluation-of-mb12066-an-nqo1-substrate
#7
Hae Won Lee, Sook Jin Seong, Boram Ohk, Woo Youl Kang, Mi-Ri Gwon, Bo Kyung Kim, Hyun-Ju Kim, Young-Ran Yoon
OBJECTIVE: This study evaluated the pharmacokinetics (PKs) and safety of a newly developed β-lapachone (MB12066) tablet, a natural NAD(P)H:quinone oxidoreductase 1 (NQO1) substrate, in healthy male volunteers. METHODS: In a randomized, double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or placebo was given twice daily for 8 days to groups of eight or three fasted healthy male subjects, respectively, followed by serial blood sampling. Plasma concentrations for β-lapachone were determined using liquid chromatography-tandem mass spectrometry...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29054567/hydrogen-sulfide-specifically-alters-nad-p-h-quinone-dehydrogenase-1-nqo1-olfactory-neurons-in-the-rat
#8
Fumiaki Imamura, Timothy K Cooper, Sanae Hasegawa-Ishii, Takashi Sonobe, Philippe Haouzi
The regions of the olfactory epithelium affected by hydrogen sulfide (H2S) toxicity in the rat present a striking similarity with the developmental olfactory zone 1 described in the mouse. This zone which is the only region containing neurons expressing NAD(P)H quinone dehydrogenase 1 (NQO1) is involved in complex behavioral responses in rodents, and other mammals, triggered by specific olfactory stimuli. We therefore sought to determine whether (1) olfactory neurons expressing NQO1 are located in the same regions in the rats and in the mice and (2) there is an overlap between olfactory neurons expressing this protein and those affected by the toxicity of H2S...
October 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/29053632/protective-effect-of-flavonoids-from-ziziphus-jujuba-cv-jinsixiaozao-against-acetaminophen-induced-liver-injury-by-inhibiting-oxidative-stress-and-inflammation-in-mice
#9
Weizhen Huang, Yongjie Wang, Xiaoyan Jiang, Yueyue Sun, Zhongxi Zhao, Siying Li
This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29018782/comparison-of-blueberry-vaccinium-spp-and-vitamin-c-via-antioxidative-and-epigenetic-effects-in-human
#10
Minju Kim, Hyunkyung Na, Hiroshi Kasai, Kazuaki Kawai, Yun-Shan Li, Mihi Yang
BACKGROUND: Chemopreventive effects and the underlying mechanisms of blueberry (Vaccinium spp.) are not clearly understood in human. We hypothesized blueberry would work via antioxidative and epigenetic modulation, which is similar to vitamin C. METHODS: We performed a pilot and non-inferiority study in healthy young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine, and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1 (NQO1), methylenetetrahydrofolate reductase (MTHFR), or DNA methyltransferase 1 (DNMT1) genes in their blood...
September 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29017857/administration-of-5-methoxyindole-2-carboxylic-acid-that-potentially-targets-mitochondrial-dihydrolipoamide-dehydrogenase-confers-cerebral-preconditioning-against-ischemic-stroke-injury
#11
Jinzi Wu, Rongrong Li, Wenjun Li, Ming Ren, Nopporn Thangthaeng, Nathalie Sumien, Ran Liu, Shaohua Yang, James W Simpkins, Michael J Forster, Liang-Jun Yan
The objective of this study was to investigate a possible role of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as a chemical preconditioning target for neuroprotection against ischemic injury. We used 5-methoxyindole-2-carboxylic acid (MICA), a reportedly reversible DLDH inhibitor, as the preconditioning agent and administered MICA to rats mainly via dietary intake. Upon completion of 4 week's MICA treatment, rats underwent 1h transient ischemia and 24h reperfusion followed by tissue collection. Our results show that MICA protected the brain against ischemic stroke injury as the infarction volume of the brain from the MICA-treated group was significantly smaller than that from the control group...
October 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28982598/methyleugenol-protects-against-t-bhp-triggered-oxidative-injury-by-induction-of-nrf2-dependent-on-ampk-gsk3%C3%AE-and-erk-activation
#12
Junfeng Zhou, Xiaoyuan Ma, Yan Cui, Yang Song, Lei Yao, Yuanyuan Liu, Shanshan Li
Methyleugenol (Mlg), a natural ingredient of many herbs and used as a flavoring substance in dietary products, inhibits inflammation and oxidative stress. The aim of the study is to explore the antioxidative potential of Mlg against tert-butyl hydroperoxide (t-BHP)-triggered oxidative injury and the involvement of antioxidative mechanisms. Our findings indicated that Mlg exposure significantly alleviated t-BHP-stimulated cytotoxicity, suppressed reactive oxygen species (ROS) generation, and increased superoxide dismutase (SOD) and glutathione (GSH) levels, which were related to the induction of the glutamate-cysteine ligase catalytic/modifier (GCLC/GCLM) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1) largely dependent upon upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) induction, inhibiting the Keap1 protein expression, and heightening the antioxidant response element (ARE) activity...
September 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28947488/treatment-with-sulforaphane-produces-antinociception-and-improves-morphine-effects-during-inflammatory-pain-in-mice
#13
Alejandro Redondo, Pablo Aníbal Ferreira Chamorro, Gabriela Riego, Sergi Leánez, Olga Pol
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ-opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain...
December 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28946766/salvia-miltiorrhiza-lipophilic-fraction-attenuates-oxidative-stress-in-diabetic-nephropathy-through-activation-of-nuclear-factor-erythroid-2-related-factor-2
#14
Lin An, Mei Zhou, Faiz M M T Marikar, Xue-Wen Hu, Qiu-Yun Miao, Ping Li, Jun Chen
Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28939896/mir-155-mediates-arsenic-trioxide-resistance-by-activating-nrf2-and-suppressing-apoptosis-in-lung-cancer-cells
#15
Shiyan Gu, Yanhao Lai, Hongyu Chen, Yuan Liu, Zunzhen Zhang
Arsenic trioxide (ATO) resistance is a challenging problem in chemotherapy. However, the underlying mechanisms remain to be elucidated. In this study, we identified a high level of expression of miR-155 in a human lung adenocarcinoma A549R cell line that is highly resistant to ATO. We showed that the high level of miR-155 was associated with increased levels of cell survival, colony formation, cell migration and decreased cellular apoptosis, and this was mediated by high levels of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and a high ratio of Bcl-2/Bax...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#16
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 characterize 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 utilizing toxicological and metabolomic approaches...
October 16, 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
#17
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 and then peroxide formation, which damages DNA and causes hyperactivation of poly(ADP-ribose) polymerase, resulting in extensive NAD(+)/ATP depletion...
November 3, 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
#18
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
#19
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
#20
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
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