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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/28298215/nrf2-signaling-increases-expression-of-atp-binding-cassette-subfamily-c-mrna-transcripts-at-the-blood-brain-barrier-following-hypoxia-reoxygenation-stress
#1
Kathryn Ibbotson, Joshua Yell, Patrick T Ronaldson
BACKGROUND: Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model...
March 16, 2017: Fluids and Barriers of the CNS
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/28278681/in-vitro-assessment-of-the-indirect-antioxidant-activity-of-sulforaphane-in-redox-imbalance-vanadium-induced
#3
Giuseppa Visalli, Alessio Facciolà, Maria Paola Bertuccio, Isa Picerno, Angela Di Pietro
Owing to sulforaphane presence, a dietary consumption of Brassicaceae prevents chronic diseases. This hormetic compound induces adaptive stress response at subtoxic doses, while doses that exceed the cellular defence are toxic. In HepG2, Caco-2 and Vero cells, we investigated the sulforaphane (SFN) (5 μM) role in counteracting redox imbalance induced by VOSO4 [V(IV)]. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test showed a dose-dependent viability reduction (r < -0.95; p < 0...
February 8, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#4
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28209760/glucoraphanin-ameliorates-obesity-and-insulin-resistance-through-adipose-tissue-browning-and-reduction-of-metabolic-endotoxemia-in-mice
#5
Naoto Nagata, Liang Xu, Susumu Kohno, Yusuke Ushida, Yudai Aoki, Ryohei Umeda, Nobuo Fuke, Fen Zhuge, Yinhua Ni, Mayumi Nagashimada, Chiaki Takahashi, Hiroyuki Suganuma, Shuichi Kaneko, Tsuguhito Ota
Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice...
February 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28191275/sulforaphane-prevents-angiotensin-ii-induced-testicular-cell-death-via-activation-of-nrf2
#6
Yonggang Wang, Hao Wu, Ying Xin, Yang Bai, Lili Kong, Yi Tan, Feng Liu, Lu Cai
Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28151586/nuclear-erythroid-2-related-factor-2-activation-inhibits-house-dust-mite-induced-sinonasal-epithelial-cell-barrier-dysfunction
#7
Nyall R London, Anuj Tharakan, Andrew P Lane, Shyam Biswal, Murugappan Ramanathan
BACKGROUND: Dysregulated sinonasal epithelial cell (SNEC) barrier function has been proposed to contribute to the pathogenesis of sinonasal inflammatory conditions such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Allergens such as house dust mite (HDM) have been reported to disrupt SNEC barrier integrity. We have recently identified nuclear erythroid 2-related factor 2 (Nrf2) activation via sulforaphane (SFN) stimulation to stabilize SNEC barrier function. The purpose of this study was to explore whether Nrf2 activation could ameliorate HDM-induced SNEC barrier dysfunction...
February 2, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28115273/ablation-of-akt2-prevents-paraquat-induced-myocardial-mitochondrial-injury-and-contractile-dysfunction-role-of-nrf2
#8
Shuyi Wang, Xiaoling Zhu, Lize Xiong, Jun Ren
Paraquat is a quaternary nitrogen herbicide triggering oxidative stress, mitochondrial damage and multi-organ injuries including hearts. To date, effective measure to combat paraquat toxicity is still lacking. Recent evidence has revealed a role for Akt in cardiac homeostasis. To this end, this study was designed to examine the role of Akt2 in acute paraquat exposure-induced cardiac contractile and mitochondrial injury using a unique murine model of Akt2 knockout. Cardiac contractile and intracellular Ca(2+) properties were evaluated...
March 5, 2017: Toxicology Letters
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
#9
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
#10
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
#11
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
#12
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...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27982105/nrf2-inhibits-epithelial-mesenchymal-transition-by-suppressing-snail-expression-during-pulmonary-fibrosis
#13
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
#14
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
#15
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 (SFN) prevented diabetic cardiomyopathy in both type 1 and type 2 diabetes (T2DM) animal models via the upregulation of nuclear transcription factor erythroid 2-related factor 2 (Nrf2) and metallothionein (MT). In this study, we tested whether SFN protects the heart from T2DM directly through Nrf2, MT, or both. Using Nrf2-knockout (KO), MT-KO, and wild-type (WT) mice, T2DM was induced by feeding a high-fat diet for 3 months followed by a small dose of streptozotocin. Age-matched controls were given a normal diet...
February 2017: Diabetes
https://www.readbyqxmd.com/read/27889639/sulforaphane-is-a-nrf2-independent-inhibitor-of-mitochondrial-fission
#16
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...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/27868087/diabetic-wound-healing-and-activation-of-nrf2-by-herbal-medicine
#17
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
#18
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
#19
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
#20
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
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