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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/28062182/exposure-of-airway-epithelial-cells-to-pseudomonas-aeruginosa-biofilm-derived-quorum-sensing-molecules-decrease-the-activity-of-the-anti-oxidant-response-element-bound-by-nrf2
#1
Lucie Roussel, Simon Rousseau
Chronic bacterial infections in cystic fibrosis lung disease are often characterized by Pseudomonas aeruginosa biofilms that are regulated by bacterial intercellular signals termed quorum sensing (QS), such as N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL). This study reports that biofilm-derived exoproducts decrease the transcriptional activity of the anti-oxidant response element in bronchial epithelial cells. In a live co-culture assay of BEAS-2B cells and P. aeruginosa biofilm, the QS molecule 3OC12-HSL was an important but not sole contributor to the inhibition of basal NRF2 luciferase reporter activity...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28011874/activation-of-nrf2-reduces-uva-mediated-mmp-1-upregulation-via-mapk-ap-1-signaling-cascades-the-photoprotective-effects-of-sulforaphane-and-hispidulin
#2
Anyamanee Chaiprasongsuk, Jinaphat Lohakul, Kitipong Soontrapa, Somponnat Sampattavanich, Pravit Akarasereenont, Uraiwan Panich
Ultraviolet A (UVA) irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds which can activate Nrf2, a transcription factor regulating antioxidant gene expression, should therefore serve as effective anti-photoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of MAPK/AP-1 signaling using human keratinocyte cell line (HaCaT)...
December 23, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28001083/nrf2-targeting-by-sulforaphane-a-potential-therapy-for-cancer-treatment
#3
Maria Russo, Carmela Spagnuolo, Gian Luigi Russo, Krystyna Skalicka-Woźniak, Maria Daglia, Eduardo Sobarzo-Sánchez, Seyed Fazel Nabavi, Seyed Mohammad Nabavi
In the past decades, extensive studies have reported the potential chemopreventive activity of sulforaphane, an isothiocyanate derived from glucoraphanin, occurring in large amounts in Brassica genus plants. Sulforaphane was found to be active against several forms of cancer. A growing body of data shows that sulforaphane acts against cancer at different levels, from development to progression, through pleiotropic effects. In this review, we discuss the available experimental and clinical data on the potential therapeutic role of sulforaphane against cancer...
December 21, 2016: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/27993529/sulforaphane-induces-differential-modulation-of-mitochondrial-biogenesis-and-dynamics-in-normal-cells-and-tumor-cells
#4
Mario Negrette-Guzmán, Sara Huerta-Yepez, Mario I Vega, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Omar Noel Medina-Campos, Esteban Rodríguez, Edilia Tapia, José Pedraza-Chaverri
Antioxidant-based chemotherapy has been intensely debated. Herein, we show that sulforaphane (SFN) induced mitochondrial biogenesis followed by mitochondrial fusion in a kidney cell line commonly used in nephroprotective models. At the same concentration and exposure time, SFN induced cell death in prostate cancer cells accompanied by mitochondrial biogenesis and fragmentation. Stabilization of the nuclear factor E2-related factor-2 (Nrf2) could be associated with these effects in the tumor cell line. An increase in the peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) level and a decrease in the hypoxia-inducible factor-1α (HIF1α) level would suggest a possible metabolic shift...
December 18, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27982105/nrf2-inhibits-epithelial-mesenchymal-transition-by-suppressing-snail-expression-during-pulmonary-fibrosis
#5
Wencheng Zhou, Xiaoting Mo, Wenhui Cui, Zhihui Zhang, Delin Li, Liucheng Li, Liang Xu, Hongwei Yao, Jian Gao
Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2(-/-)) and wild-type mice to compare the development of PF...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911093/dna-microarray-profiling-highlights-nrf2-mediated-chemoprevention-targeted-by-wasabi-derived-isothiocyanates-in-hepg2-cells
#6
Phoebe Zapanta Trio, Atsuyoshi Kawahara, Shunsuke Tanigawa, Kozue Sakao, De-Xing Hou
6-MSITC and 6-MTITC are sulforaphane (SFN) analogs found in Japanese Wasabi. As we reported previously, Wasabi isothiocyanates (ITCs) are activators of Nrf2-antioxidant response element pathway, and also inhibitors of pro-inflammatory cyclooxygenase-2. This study is the first to assess the global changes in transcript levels by Wasabi ITCs, comparing with SFN, in HepG2 cells. We performed comparative gene expression profiling by treating HepG2 cells with ITCs, followed by DNA microarray analyses using HG-U133 plus 2...
January 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/27903744/metallothionein-is-downstream-of-nrf2-and-partially-mediates-sulforaphane-prevention-of-diabetic-cardiomyopathy
#7
Junlian Gu, Yanli Cheng, Hao Wu, Lili Kong, Shudong Wang, Zheng Xu, Zhiguo Zhang, Yi Tan, Bradley B Keller, Honglan Zhou, Yuehui Wang, Zhonggao Xu, Lu Cai
We have reported that sulforaphane prevented diabetic cardiomyopathy in both T1DM and T2DM animal models via the up-regulation of Nrf2 and metallothionein (MT). Here we tested whether sulforaphane protects the heart from T2DM directly through Nrf2, MT or both. Using Nrf2-knockout (KO), MT-KO, and wild-type mice T2DM was induced by feeding high-fat diet (HFD) for 3 months followed by a small dose of streptozotocin. Age-matched controls were given normal diet (ND). Both T2DM and control mice were then treated with or without sulforaphane for 4 months with continually feeding HFD or ND...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27889639/sulforaphane-is-a-nrf2-independent-inhibitor-of-mitochondrial-fission
#8
Gary B O'Mealey, William L Berry, Scott M Plafker
The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1...
November 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/27868087/diabetic-wound-healing-and-activation-of-nrf2-by-herbal-medicine
#9
Donald R Senger, Shugeng Cao
Nrf2 defense is a very important cellular mechanism to control oxidative stress, which is implicated in wound healing. Nrf2 can induce many cytoprotective genes, including HO-1, NQO1 and G6PD. Among many natural products that have been reported as Nrf2 activators, sulforaphane and curcumin have been studied more widely than any others, and both are in clinical trials for non-cancerous disorders. Recently, we reported 4-ethyl catechol and 4-vinyl catechol as Nrf2 co-factors that can induce Nrf2 as potently as sulforaphane and curcumin...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27860235/a-functional-pseudogene-nmral2p-is-regulated-by-nrf2-and-serves-as-a-coactivator-of-nqo1-in-sulforaphane-treated-colon-cancer-cells
#10
Gavin S Johnson, Jia Li, Laura M Beaver, W Mohaiza Dashwood, Deqiang Sun, Praveen Rajendran, David E Williams, Emily Ho, Roderick H Dashwood
SCOPE: The anticancer agent sulforaphane (SFN) acts via multiple mechanisms to modulate gene expression, including the induction of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent signaling and the inhibition of histone deacetylase activity. Transcriptomics studies were performed in SFN-treated human colon cancer cells and in nontransformed colonic epithelial cells in order to pursue new mechanistic leads. METHODS AND RESULTS: RNA-sequencing corroborated the expected changes in cancer-related pathways after SFN treatment...
November 18, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27847555/sulforaphane-protects-pancreatic-acinar-cell-injury-by-modulating-nrf2-mediated-oxidative-stress-and-nlrp3-inflammatory-pathway
#11
Zhaojun Dong, Haixiao Shang, Yong Q Chen, Li-Long Pan, Madhav Bhatia, Jia Sun
Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27847240/inflammation-and-airway-hyperresponsiveness-after-chlorine-exposure-are-prolonged-by-nrf2-deficiency-in-mice
#12
Satoshi Ano, Alice Panariti, Benoit Allard, Michael O'Sullivan, Toby K McGovern, Yoichiro Hamamoto, Yukio Ishii, Masayuki Yamamoto, William S Powell, James G Martin
RATIONALE: Chlorine gas (Cl2) is a potent oxidant and trigger of irritant induced asthma. We explored NF-E2-related factor 2 (Nrf2)-dependent mechanisms in the asthmatic response to Cl2, using Nrf2-deficient mice, buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis and sulforaphane (SFN), a phytochemical regulator of Nrf2. METHODS: Airway inflammation and airway hyperresponsiveness (AHR) were assessed 24 and 48h after a 5-min nose-only exposure to 100ppm Cl2 of Nrf2-deficient and wild type Balb/C mice treated with BSO or SFN...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27833054/prophylactic-effects-of-sulforaphane-on-depression-like-behavior-and-dendritic-changes-in-mice-after-inflammation
#13
Ji-Chun Zhang, Wei Yao, Chao Dong, Chun Yang, Qian Ren, Min Ma, Mei Han, Jin Wu, Yusuke Ushida, Hiroyuki Suganuma, Kenji Hashimoto
Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27832073/lack-of-effect-of-oral-sulforaphane-administration-on-nrf2-expression-in-copd-a-randomized-double-blind-placebo-controlled-trial
#14
Robert A Wise, Janet T Holbrook, Gerard Criner, Sanjay Sethi, Sobharani Rayapudi, Kuladeep R Sudini, Elizabeth A Sugar, Alyce Burke, Rajesh Thimmulappa, Anju Singh, Paul Talalay, Jed W Fahey, Charles S Berenson, Michael R Jacobs, Shyam Biswal
BACKGROUND: COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2). METHODS: This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers. Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27824068/sulforaphane-improves-ischemia-induced-detrusor-overactivity-by-downregulating-the-enhancement-of-associated-endoplasmic-reticulum-stress-autophagy-and-apoptosis-in-rat-bladder
#15
Huai-Ching Tai, Shiu-Dong Chung, Chiang-Ting Chien, Hong-Jeng Yu
Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27778243/activation-of-the-nuclear-factor-e2-related-factor%C3%A2-2-anitioxidant-response-element-alleviates-the-nitroglycerin-induced-hyperalgesia-in-rats
#16
Wei Di, Xiaolei Shi, Hua Lv, Jun Liu, Hong Zhang, Zhiwei Li, Yannan Fang
BACKGROUND: Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. METHODS: The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27774770/protection-of-nrf2-against-arsenite-induced-oxidative-damage-is-regulated-by-the-cyclic-guanosine-monophosphate-protein-kinase-g-signaling-pathway
#17
Chengzhi Chen, Xuejun Jiang, Shiyan Gu, Yanhao Lai, Yuan Liu, Zunzhen Zhang
Arsenite has been shown to induce a variety of oxidative damage in mammalian cells. However, the mechanisms underlying cellular responses to its adverse effects remain unknown. We previously showed that the level of Nrf2, a nuclear transcription factor significantly increased in arsenite-treated human bronchial epithelial (HBE) cells suggesting that Nrf2 is involved in responding to arsenite-induced oxidative damage. To explore how Nrf2 can impact arsenite-induced oxidative damage, in this study, we examined Nrf2 activation and its regulation upon cellular arsenite exposure as well as its effects on arsenite-induced oxidative damage in HBE cells...
October 24, 2016: Environmental Toxicology
https://www.readbyqxmd.com/read/27727176/sulforaphane-prevents-testicular-damage-in-kunming-mice-exposed-to-cadmium-via-activation-of-nrf2-are-signaling-pathways
#18
Shu-Hua Yang, Miao Long, Li-Hui Yu, Lin Li, Peng Li, Yi Zhang, Yang Guo, Feng Gao, Ming-Da Liu, Jian-Bin He
Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations...
October 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27717869/withaferin-a-induces-nrf2-dependent-protection-against-liver-injury-role-of-keap1-independent-mechanisms
#19
Dushani L Palliyaguru, Dionysios V Chartoumpekis, Nobunao Wakabayashi, John J Skoko, Yoko Yagishita, Shivendra V Singh, Thomas W Kensler
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models...
December 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27702566/oxidative-damage-control-in-a-human-mini-organ-nrf2-activation-protects-against-oxidative-stress-induced-hair-growth-inhibition
#20
Iain S Haslam, Laura Jadkauskaite, Imre Lőrinc Szabó, Selma Staege, Jasper Hesebeck-Brinckmann, Gail Jenkins, Ranjit K Bhogal, Fei-Ling Lim, Nilofer Farjo, Bessam Farjo, Tamás Bíró, Matthias Schäfer, Ralf Paus
The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the "master regulator" of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles...
October 1, 2016: Journal of Investigative Dermatology
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