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Nrf2 AND NQO1

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https://www.readbyqxmd.com/read/29339024/nrf2-are-pathway-attenuates-oxidative-and-apoptotic-response-in-human-osteoarthritis-chondrocytes-by-activating-erk1-2-elk1-p70s6k-p90rsk-signaling-axis
#1
Nazir M Khan, Imran Ahmad, Tariq M Haqqi
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1β stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient...
January 12, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29328656/design-and-synthesis-of-novel-reactive-oxygen-species-inducers-for-the-treatment-of-pancreatic-ductal-adenocarcinoma
#2
Yuting Kuang, Mario Sechi, Salvatore Nurra, Mats Ljungman, Nouri Neamati
Altering redox homeostasis provides distinctive therapeutic opportunities for the treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox modulators that we previously showed to induce potent growth inhibition in pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization campaign yielded QD325 as the most potent redox modulator candidate inducing substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing following treatments with the QD compounds revealed induction of stress responses in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29304479/microrna-140-5p-aggravates-doxorubicin-induced-cardiotoxicity-by-promoting-myocardial-oxidative-stress-via-targeting-nrf2-and-sirt2
#3
Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29285281/activation-of-nrf2-by-mind4-17-protects-osteoblasts-from-hydrogen-peroxide-induced-oxidative-stress
#4
Shiguang Guo, Hao-Dong Fei, Feng Ji, Feng-Li Chen, Yue Xie, Shou-Guo Wang
MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (H2O2)-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by H2O2. MIND4-17 treatment induced Keap1-Nrf2 disassociation, causing Nrf2 stabilization, accumulation and nuclear translocation in osteoblasts, leading to transcription of several Nrf2-dependent genes, including heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase modifier subunit (GCLM) and catalytic subunit (GCLC)...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282639/estrogen-dependent-nrf2-expression-protects-against-reflux-induced-esophagitis
#5
Yudai Torihata, Kiyotaka Asanuma, Katsunori Iijima, Tetsuhiko Mikami, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa
BACKGROUND: Gastroesophageal reflux disease is more common in males than in females. The enhanced antioxidative capacity of estrogen in females might account for the gender difference. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in the host defense mechanism against oxidative stress. AIMS: This study aimed to clarify the role of Nrf2 in reflux-induced esophageal inflammation, focusing on the gender difference and nitric oxide. METHODS: Gastroesophageal reflux was surgically induced in male and female rats...
December 27, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29248571/the-secondary-fusarium-metabolite-aurofusarin-induces-oxidative-stress-cytotoxicity-and-genotoxicity-in-human-colon-cells
#6
Katharina Jarolim, Konstantin Wolters, Lydia Woelflingseder, Gudrun Pahlke, Julia Beisl, Hannes Puntscher, Dominik Braun, Michael Sulyok, Benedikt Warth, Doris Marko
Aurofusarin (AURO), a dimeric naphthoquinone, is produced by Fusarium fungi. Although frequently found in food and feed, toxicological studies are limited. Hence, the in vitro toxicity of AURO was investigated in the colon adenocarcinoma cell line HT29 and the non-tumorigenic colon cells HCEC-1CT. Cytotoxic effects were found at concentrations ≥1 μM by evaluating mitochondrial activity (WST-1) and cellular proliferation (sulforhodamine B assay). 10 μM of AURO induced a decrease of cells in the S-phase, measured by flow cytometry...
December 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29247614/mechanism-implicated-in-the-anti-allodynic-and-anti-hyperalgesic-effects-induced-by-the-activation-of-heme-oxygenase-1-carbon-monoxide-signaling-pathway-in-the-central-nervous-system-of-mice-with-neuropathic-pain
#7
Gabriela Riego, Alejandro Redondo, Sergi Leánez, Olga Pol
The administration of a carbon monoxide-releasing compound (tricarbonyldichlororuthenium(II)dimer, CORM-2) or an heme oxygenase 1 (HO-1) inductor (cobalt protoporphyrin IX, CoPP) exerts potent antinociceptive effects during chronic pain, but their actions in the central nervous system of animals with neuropathic pain have not been evaluated. Our objective is to investigate the effects of these treatments on the oxidative, inflammatory and molecular changes induced by sciatic nerve injury in several brain areas...
December 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29247555/the-triterpenoid-corosolic-acid-blocks-transformation-and-epigenetically-reactivates-nrf2-in-tramp-c1-prostate-cells
#8
Jie Yang, Renyi Wu, Wenji Li, Linbo Gao, Yuqing Yang, Ping Li, Ah-Ng Kong
Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells...
December 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29247444/effect-of-arsenic-exposure-on-nrf2-keap1-pathway-and-epigenetic-modification
#9
Beata Janasik, Edyta Reszka, Magdalena Stanislawska, Ewa Jablonska, Renata Kuras, Edyta Wieczorek, Beata Malachowska, Wojciech Fendler, Wojciech Wasowicz
Arsenic (As) is a known toxic element and carcinogen. Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant genes in response to redox stress. To explore associations between As level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 61 occupationally exposed men with median (Me) age 50 years (interquartile range (IQR) 42-54) and in a control group of 52 men aged 40 (IQR 31-51...
December 15, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29243436/-effect-of-neoflavonoid-latifolin-isolated-from-dalbergia-odorifera-on-acute-myocardial-ischemia-in-rats-and-its-mechanism-of-nrf2-signaling-pathway
#10
Xue-Liang Li, Lan-Ying Chen, Zi-Yi Guan, Yao Luo, Ya-Ru Cui, Rong-Hua Liu, Feng Shao, Ding-Qing Wang
The present study was designed to evaluate the cardioprotective effect of latifolin on pituitrin(Pit) or isoproterenol(ISO)-induced myocardial injury in rats, and further investigate its underlying mechanisms. Rats were administrated sublingually with pituitrin or subcutaneously with isoproterenol to induce acute myocardial ischemia in rats, and lead II electrocardiograph was recorded. In rats with isoproterenol, ELISA assay or colorimetric method was used to detect the content or activity of myocardial injury markers in serum, and the SOD activity and MDA content in myocardium were detected by colorimetric assay; histopathological examination was conducted by HE staining; the frozen section of myocardial tissues was used for DCFH-DA fluorescent staining to detect the content of ROS in myocardium; Western blot was used to detect the protein expression levels of Nrf2, Keap1, HO-1 and NQO1 in myocardium...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29241092/trehalose-protects-against-oxidative-stress-by-regulating-the-keap1-nrf2-and-autophagy-pathways
#11
Yuhei Mizunoe, Masaki Kobayashi, Yuka Sudo, Shukoh Watanabe, Hiromine Yasukawa, Daiki Natori, Ayana Hoshino, Arisa Negishi, Naoyuki Okita, Masaaki Komatsu, Yoshikazu Higami
Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear...
September 20, 2017: Redox Biology
https://www.readbyqxmd.com/read/29225188/rosuvastatin-improves-myocardial-hypertrophy-after-hemodynamic-pressure-overload-via-regulating-the-crosstalk-of-nrf2-are-and-tgf-%C3%AE-smads-pathways-in-rat-heart
#12
Pengbo Wang, Lin Luo, Qiusheng Shen, Gaoyong Shi, Anaz Mohammed, Songshi Ni, Xiang Wu
Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor β (TGF-β) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-β1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29221138/gas-signaling-molecule-hydrogen-sulfide-attenuates-doxorubicin-induced-dilated-cardiomyopathy
#13
Zongliang Yu, Wei Zhang, Mengyao Zhang, Mengchao Jin, Weiting Xu, Xiang Zhou
Increasing evidence has revealed that hydrogen sulfide (H2S) has beneficial effects in the treatment of various cardiovascular diseases. However, whether H2S can attenuate the development of dilated cardiomyopathy (DCM) remains unclear. In this study, we generated a rat model of DCM induced by doxorubicin and investigated the protective effects of H2S against DCM. Cardiac structure and function were analyzed by two-dimensional echocardiography. Oxidative stress was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29214656/screening-active-components-of-modified-xiaoyao-powder-as-nrf2-agonists
#14
Yujie Yang, Yanran Wang, Ting Wang, Xuehua Jiang, Ling Wang
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) regulates antioxidant enzymes and phase II detoxifying enzymes, such as NAD(P)H: quinone oxidoreductase 1 (NQO1). Modified Xiaoyao powder (MXP) is most frequently used in the prevention and treatment of breast cancer in China. This study aimed to screen active components of MXP for antioxidant stress and chemoprevention, which depend on NRF2-NQO1 signalling pathway. A total of 25 monomeric compounds contained in MXP were screened using an antioxidant response element-luciferase reporter...
December 7, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29210649/sargassum-fusiforme-polysaccharide-rejuvenates-the-small-intestine-in-mice-through-altering-its-physiology-and-gut-microbiota-composition
#15
P Chen, S Yang, C Hu, Z Zhao, J Liu, Y Cheng, S Wang, Q Chen, P Yu, X Zhang, M Wu
BACKGROUND AND OBJECTIVE: Aging can result in a progressive decline in cellular protection and physiological function. The physiological status and microbiota of the intestine are intensively linked to the aging process. Numerous studies have suggested that Sargassum fusiforme polysaccharides possess antioxidant and anti-aging activities. However, it remains unclear as to whether S. fusiforme polysaccharides can prevent the insult of oxidant and aging through modulating the physiological status and microbiota of the intestine...
December 4, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29191105/curcumin-and-its-derivatives-inhibit-2-3-7-8-tetrachloro-dibenzo-p-dioxin-induced-expression-of-drug-metabolizing-enzymes-through-aryl-hydrocarbon-receptor-mediated-pathway
#16
Rika Nakai, Shun Fukuda, Masaya Kawase, Yoko Yamashita, Hitoshi Ashida
Certain dioxins, including 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD), are exogenous ligands for an aryl hydrocarbon receptor (AhR) and induces various drug-metabolizing enzymes. In this study, we examined the effect of curcumin on expression of drug-metabolizing enzymes through the AhR and NF-E2 related factor 2 (Nrf2) pathways. Curcumin dose-dependently inhibited TCDD-induced expression of phase I enzyme cytochrome P450 1A1 (CYP1A1) and phase II enzymes NAD(P)H:quinone oxidoreductase-1 (NQO1) and heme oxygenase 1 (HO-1) but not tert-butyl hydroquinone-induced NQO1 and HO-1, suggesting that curcumin inhibited only AhR pathway, but not Nrf2 one directly...
December 1, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29180269/dysregulation-of-antioxidant-responses-in-patients-diagnosed-with-concomitant-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#17
Colin T Shearn, David J Orlicky, Dennis R Petersen
OBJECTIVE: Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease that is characterized by severe peri-biliary tract inflammation and fibrosis, elevated oxidative stress and hepatocellular injury. A hallmark of PSC patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in approximately 70%-80% of PSC patients (PSC/IBD). The objective of this study was to determine the impact of end stage PSC/IBD on cellular antioxidant responses and the formation of protein carbonylation...
November 24, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29176993/an-excess-dietary-vitamin-e-concentration-does-not-influence-nrf2-signaling-in-the-liver-of-rats-fed-either-soybean-oil-or-salmon-oil
#18
Klaus Eder, Marina Siebers, Erika Most, Susan Scheibe, Norbert Weissmann, Denise K Gessner
Background: Reactive oxygen species (ROS) are known to stimulate the activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), the key regulator of the antioxidant and cytoprotective defense system in the body. The hypothesis underlying this study was that high dietary concentrations of vitamin E suppress Nrf2 activation, and thus could weaken the body's antioxidative and cytoprotective capacity. As the effect of vitamin E on Nrf2 pathway might be influenced by concentrations of fatty acids susceptible to oxidation in the diet, we used also diets containing either soybean oil as a reference oil or salmon oil as a source of oil rich in n-3 polyunsatuated fatty acids...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29172017/scutellarin-prevents-nonalcoholic-fatty-liver-disease-nafld-and-hyperlipidemia-via-pi3k-akt-dependent-activation-of-nuclear-factor-erythroid-derived-2-like-2-nrf2-in-rats
#19
Hua Fan, Xiande Ma, Peng Lin, Qiang Kang, Zhilong Zhao, Lina Wang, Dan Sun, Jiayi Cheng, Yajun Li
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing...
November 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29163788/mind4-17-protects-retinal-pigment-epithelium-cells-and-retinal-ganglion-cells-from-uv
#20
Chaopeng Li, Kang Yan, Wenqi Wang, Qing Bai, Changming Dai, Xiaofeng Li, Darui Huang
Nrf2 activation would efficiently protect retinal cells from UV radiation (UVR). Recent studies have developed a Nrf2-targeting thiazole-containing compound MIND4-17, which activates Nrf2 through blocking its association with Keap1. In the current study, we demonstrated that pretreatment with MIND4-17 efficiently protected retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs) from UVR. UVR-induced apoptosis in the retinal cells was also largely attenuated by MIND4-17 pretreatment. MIND4-17 presumably separated Nrf2 from Keap1, allowing its stabilization and accumulation in retinal cells, which then translocated to cell nuclei and promoted transcription of ARE-dependent anti-oxidant genes, including HO1, NQO1 and GCLM...
October 27, 2017: Oncotarget
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