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Nrf2 AND NQO1

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https://www.readbyqxmd.com/read/28300285/hx-1171-a-novel-nrf2-activator-induces-nqo1-and-hmox1-expression
#1
Jimin Kim, Su-Hyun Shin, Young-Eun Ko, Tokutaro Miki, Heung-Mo Bae, Jong-Koo Kang, Jae Wha Kim
HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a novel synthesized vitamin E derivative, which reportedly has positive effects on various diseases and conditions, such as liver fibrosis, hepatic cirrhosis, and cancer. In this study, we analyzed the transcriptional activity induced by HX-1171. Results from reverse transcription polymerase chain reaction and promoter assays reveal that HX-1171 increased the expression of NQO1 and HMOX1, encoding antioxidant-related enzymes, in A549 human lung epithelial cells...
March 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28295950/sulforaphane-attenuates-di-n-butylphthalate-induced-reproductive-damage-in-pubertal-mice-involvement-of-the-nrf2-antioxidant-system
#2
Xu-Ping Jiang, Jing-Yuan Tang, Zhen Xu, Peng Han, Zhi-Qiang Qin, Cheng-di Yang, Shang-Qian Wang, Min Tang, Wei Wang, Chao Qin, Yang Xu, Bai-Xin Shen, Wei-Min Zhou, Wei Zhang
di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis...
March 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28283797/influence-of-nrf2-activators-on-subcellular-skeletal-muscle-protein-and-dna-synthesis-rates-after-6%C3%A2-weeks-of-milk-protein-feeding-in-older-adults
#3
Adam R Konopka, Jaime L Laurin, Robert V Musci, Christopher A Wolff, Justin J Reid, Laurie M Biela, Qian Zhang, Fredrick F Peelor, Christopher L Melby, Karyn L Hamilton, Benjamin F Miller
In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding...
March 10, 2017: Geroscience
https://www.readbyqxmd.com/read/28274305/-protective-effect-of-quercetin-against-immunological-liver-injury-through-activating-nrf2-are-signaling-pathway
#4
Caibing Wei, Liandi Zhou, Yuzhen Zhang, Jiawei Zhang, Qihui Zhang, Kun Tao
Objective To observe the protective effect of quercetin against immunological liver injury induced by triptolide, and investigate the involvement of Nrf2/ARE signaling pathway in the protection. Methods Fifty C57BL/6J mice were randomly divided into five groups: control group, model group, (20, 50, 80) mg/kg quercetin pre-treatment groups. Each group included 10 mice. The mice were treated with different doses of quercetin once daily for consecutive 10 days. At the end of the experiment, triptolide (500 μg/kg) was given intragastrically to induce immunological liver injury in all groups except for the control group...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28254546/relb-attenuates-cigarette-smoke-extract-induced-apoptosis-in-association-with-transcriptional-regulation-of-the-aryl-hydrocarbon-receptor
#5
Matthew Iu, Michela Zago, Angela Rico de Souza, Manuella Bouttier, Swati Pareek, John H White, Qutayba Hamid, David H Eidelman, Carolyn J Baglole
Chronic obstructive pulmonary disease (COPD) is a chronic and prevalent respiratory disease caused primarily by long term inhalation of cigarette smoke. A major hallmark of COPD is elevated apoptosis of structural lung cells including fibroblasts. The NF-κB member RelB may suppress apoptosis in response to cigarette smoke, but its role in lung cell survival is not known. RelB may act as a pro-survival factor by controlling the expression of superoxide dismutase 2 (SOD2). SOD2 is also regulated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that suppresses cigarette smoke-induced apoptosis...
February 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28253885/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-activator-dh404-protects-against-diabetes-induced-endothelial-dysfunction
#6
Arpeeta Sharma, Luddwi Rizky, Nada Stefanovic, Mitchel Tate, Rebecca H Ritchie, Keith W Ward, Judy B de Haan
BACKGROUND: Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to vascular dysfunction. Nrf2, a master regulator of several anti-oxidant genes and a suppressor of inflammatory NF-κB, has potential as a target to combat oxidative stress and inflammation. The aim of this study was to investigate the effects of a novel Nrf2 activator, the bardoxolone methyl derivative dh404, on endothelial function in vitro and in vivo...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28250190/activation-of-nrf2-antioxidant-signaling-by-1-25-dihydroxycholecalciferol-prevents-leptin-induced-oxidative-stress-and-inflammation-in-human-endothelial-cells
#7
Thaisa M Teixeira, Danielly C da Costa, Angela C Resende, Christophe O Soulage, Flavia F Bezerra, Julio B Daleprane
Background: Obesity is associated with hyperleptinemia and endothelial dysfunction. Hyperleptinemia has been reported to induce both oxidative stress and inflammation by increasing reactive oxygen species production.Objective: The objective of this study was to determine the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] against leptin-induced oxidative stress and inflammation in human endothelial cells.Methods: Small interfering RNA (siRNA) were used to knock down the expression of vitamin D receptor (VDR) in human umbilical vein endothelial cells (HUVECs)...
March 1, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28249220/chloroquine-attenuates-paraquat-induced-lung-injury-in-mice-by-altering-inflammation-oxidative-stress-and-fibrosis
#8
Haitao Shen, Na Wu, Yu Wang, Hongyu Zhao, Lichun Zhang, Tiegang Li, Min Zhao
Paraquat is one of the most extensively used herbicides and has high toxicity for humans and animals. However, there is no effective treatment for paraquat poisoning. The aim of the present study was to evaluate the effects of chloroquine on paraquat-induced lung injury in mice. Mice received a single intraperitoneal injection of paraquat and a daily intraperitoneal injection of the indicated dosages of chloroquine or dexamethasone. The histological changes, inflammation and oxidative stress in the lungs were examined at day 3, and the degree of pulmonary fibrosis was examined at day 28...
February 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28246026/the-novel-nrf2-inducer-tfm-735-ameliorates-experimental-autoimmune-encephalomyelitis-in-mice
#9
Chika Higashi, Atsuko Kawaji, Naoto Tsuda, Makiko Hayashi, Ryota Saito, Yoko Yagishita, Takafumi Suzuki, Akira Uruno, Masaki Nakamura, Kazunari Nakao, Shoji Furusako, Masayuki Yamamoto
The transcription factor NF-E2-related factor 2 (Nrf2) is a key regulator of cellular defense mechanisms against oxidative stress. Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, is characterized by progressive demyelination and neurodegeneration induced by inflammation and oxidative stress. The induction of Nrf2 signaling has been shown to inhibit disease development and progression in the experimental autoimmune encephalomyelitis (EAE) model of MS in mice. In the present study, we performed a high-throughput screening assay using a chimeric construct of the N-terminal portion of Nrf2 fused to LacZ...
February 25, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28243358/hydrogen-rich-water-ameliorates-total-body-irradiation-induced-hematopoietic-stem-cell-injury-by-reducing-hydroxyl-radical
#10
Junling Zhang, Xiaolei Xue, Xiaodan Han, Yuan Li, Lu Lu, Deguan Li, Saijun Fan
We examined whether consumption of hydrogen-rich water (HW) could ameliorate hematopoietic stem cell (HSC) injury in mice with total body irradiation (TBI). The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical ((∙)OH) levels in the c-kit(+) cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs) increased and apoptotic c-kit(+) cells decreased in irradiated mice uptaken with HW...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28237856/wogonin-a-plant-derived-small-molecule-exerts-potent-anti-inflammatory-and-chondroprotective-effects-through-the-activation-of-ros-erk-nrf2-signaling-pathways-in-human-osteoarthritis-chondrocytes
#11
Nazir M Khan, Abdul Haseeb, Mohammad Y Ansari, Pratap Devarapalli, Sara Haynie, Tariq M Haqqi
Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Here, we evaluated the potential chondroprotective and anti-inflammatory effects of Wogonin, a naturally occurring flavonoid, in IL-1β-stimulated human OA chondrocytes and cartilage explants. Wogonin completely suppressed the expression and production of inflammatory mediators including IL-6, COX-2, PGE2, iNOS and NO in IL-1β-stimulated OA chondrocytes. Further, Wogonin exhibits potent chondroprotective potential by switching the signaling axis of matrix degradation from catabolic towards anabolic ends and inhibited the expression, production and activities of matrix degrading proteases including MMP-13, MMP-3, MMP-9, and ADAMTS-4 in OA chondrocytes, and blocked the release of s-GAG and COL2A1 in IL-1β-stimulated OA cartilage explants...
February 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28230744/s-allylmercaptocysteine%C3%A2-attenuates%C3%A2-cisplatin-induced%C3%A2-nephrotoxicity%C3%A2-through%C3%A2-suppression%C3%A2-of%C3%A2-apoptosis-%C3%A2-oxidative%C3%A2-stress-%C3%A2-and%C3%A2-inflammation
#12
Xiaosong Zhu, Xiaoyan Jiang, Ang Li, Zhongxi Zhao, Siying Li
Cisplatin is a potent chemotherapeutic agent, but its clinical usage is limited by nephrotoxicity. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has antioxidant and anti-inflammatory properties and plays an important role in protecting cells from apoptosis. This study aims to examine the protective effects of SAMC on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection. Rats were treated with cisplatin with or without pre-treatment with SAMC...
February 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#13
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
May 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28214984/dl-3-n-butylphthalide-nbp-provides-neuroprotection-in-the-mice-models-after-traumatic-brain-injury-via-nrf2-are-signaling-pathway
#14
Zhengwei Liu, Handong Wang, Xiaofeng Shi, Liwen Li, Mengliang Zhou, Hui Ding, Youqing Yang, Xiang Li, Ke Ding
The present study was aimed to evaluate the neuroprotective effects of NBP in the mice models of TBI, as well as the possible role of Nrf2-ARE pathways in the assumptive neuroprotection. In mice,a modified Marmarou's weight-drop model was employed to induce TBI. ICR mice were randomly assigned to four experimental groups: sham, TBI, TBI+vehicle(V) and TBI+NBP. NBP (100 mg/kg) was administered via an intraperitoneal (i.p.) injection at 1 h following TBI. The administration of NBP significantly ameliorated the effects of the brain injury, including neurological deficits, brain water content, and cortical neuronal apoptosis...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28212397/a-targeted-gene-expression-platform-allows-for-rapid-analysis-of-chemical-induced-antioxidant-mrna-expression-in-zebrafish-larvae
#15
Margaret G Mills, Evan P Gallagher
Chemical-induced oxidative stress and the biochemical pathways that protect against oxidative damage are of particular interest in the field of toxicology. To rapidly identify oxidative stress-responsive gene expression changes in zebrafish, we developed a targeted panel of antioxidant genes using the Affymetrix QuantiGene Plex (QGP) platform. The genes contained in our panel include eight putative Nrf2 (Nfe2l2a)-dependent antioxidant genes (hmox1a, gstp1, gclc, nqo1, prdx1, gpx1a, sod1, sod2), a stress response gene (hsp70), an inducible DNA damage repair gene (gadd45bb), and three reference genes (actb1, gapdh, hprt1)...
2017: PloS One
https://www.readbyqxmd.com/read/28211606/nrf2-a-novel-therapeutic-target-in-fragile-x-syndrome-is-modulated-by-nnz2566
#16
Robert M J Deacon, Michael J Hurley, Camila Martínez Rebolledo, Mike Snape, Francisco J Altimiras, Leandro Farías, Michael Pino, Rodolfo Biekofsky, Larry Glass, Patricia Cogram
Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autism. Progress in basic neuroscience has led to identification of molecular targets for treatment in FXS; however, there is a gap in translation to targeted therapies in humans. The present study introduces a novel therapeutic target for FXS: nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor known to induce expression of over 100 cytoprotective genes...
February 17, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28202547/post-translational-activation-of-glutamate-cysteine-ligase-with-dimercaprol-a-novel-mechanism-of-inhibiting-neuroinflammation-in-vitro
#17
Pallavi B McElroy, Ashwini Sri Hari, Brian J Day, Manisha Patel
Neuroinflammation and oxidative stress are hallmarks of various neurological diseases. However, whether and how the redox processes control neuroinflammation is incompletely understood. We hypothesized that increasing cellular glutathione (GSH) levels would inhibit neuroinflammation. A series of thiol compounds were identified to elevate cellular GSH levels by a novel approach i.e. post-translational activation of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH biosynthesis. These small thiolcontaining compounds were examined for their ability to increase intracellular GSH levels in a murine microglial cell line (BV2), of which dimercaprol [2,3-dimercapto-1-propanol (DMP)] was found to be the most effective compound...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#18
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/28169530/intranasal-pretreatment-with-z-ligustilide-the-main-volatile-component-of-rhizoma-chuanxiong-confers-prophylaxis-against-cerebral-ischemia-via-nrf2-and-hsp70-signaling-pathways
#19
Juan Li, Jie Yu, Hui Ma, Na Yang, Li Li, Ding-Ding Zheng, Ming-Xia Wu, Zhi-Long Zhao, Hong-Yi Qi
Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0...
February 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28157180/toxic-metabolites-mapk-and-nrf2-keap1-signaling-pathways-involved-in-oxidative-toxicity-in-mice-liver-after-chronic-exposure-to-mequindox
#20
Qianying Liu, Zhixin Lei, Anxiong Huang, Qinghua Wu, Shuyu Xie, Ihsan Awais, Menghong Dai, Xu Wang, Zonghui Yuan
Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver...
February 3, 2017: Scientific Reports
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