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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/29427794/concerted-redox-modulation-by-sulforaphane-alleviates-diabetes-and-cardiometabolic-syndrome
#1
Bijal Patel, Giovanni E Mann, Sarah J Chapple
Diabetes and cardiometabolic disorders such as hypertension and obesity are major risk factors for the development of cardiovascular disease, with a wealth of evidence suggesting that oxidative stress is linked to the initiation and pathogenesis of these disease processes. With yearly increases in the global incidence of cardiovascular diseases (CVD) and diabetes, numerous studies have focused on characterizing whether upregulating antioxidant defenses through exogenous antioxidants (e.g. vitamin E, vitamin C) or activation of endogenous defenses (e...
February 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29410668/sulforaphane-inhibits-lipopolysaccharide-induced-inflammation-cytotoxicity-oxidative-stress-and-mir-155-expression-and-switches-to-mox-phenotype-through-activating-extracellular-signal-regulated-kinase-1-2-nuclear-factor-erythroid-2-related-factor-2-antioxidant
#2
Erden Eren, Kemal Ugur Tufekci, Kamer Burak Isci, Bora Tastan, Kursad Genc, Sermin Genc
Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29382536/epigenetic-modification-of-nrf2-by-sulforaphane-increases-the-antioxidative-and-anti-inflammatory-capacity-in-a-cellular-model-of-alzheimer-s-disease
#3
Fangfang Zhao, Jianlei Zhang, Na Chang
Sulforaphane was reported to exert neuroprotective effects via upregulating expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and has received increasing attention as an alternative candidate for treatment of Alzheimer's disease (AD). However, the mechanism to account for Nrf2 upregulation by sulforaphane in AD remains unknown. Herein, we found that sulforaphane upregulated Nrf2 expression and promoted Nrf2 nuclear translocation via decreasing DNA methylation levels of the Nrf2 promoter in mouse neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APPswe cells), a cellular model of AD...
January 27, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29362432/nrf2-antioxidant-pathway-suppresses-numb-mediated-epithelial-mesenchymal-transition-during-pulmonary-fibrosis
#4
Zhihui Zhang, Jiao Qu, Cheng Zheng, Panpan Zhang, Wencheng Zhou, Wenhui Cui, Xiaoting Mo, Liucheng Li, Liang Xu, Jian Gao
Epithelial mesenchymal transition (EMT) is a key progression that promotes pulmonary fibrosis (PF). Numb, a phosphotyrosine-binding domain (PTB) protein, is implicated with EMT. Nuclear factor erythroid 2-related factor2 (Nrf2) and its downstream proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) constitute an important pathway of antioxidant defense signal for protecting against PF. It remains elusive whether Nrf2 antioxidant pathway and Numb have a potential relationship in EMT-mediated PF...
January 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29353218/sulforaphane-prevents-angiotensin-ii-induced-cardiomyopathy-by-activation-of-nrf2-via-stimulating-the-akt-gsk-3%C3%A3-fyn-pathway
#5
Ying Xin, Yang Bai, Xin Jiang, Shanshan Zhou, Yuehui Wang, Kupper A Wintergerst, Taixing Cui, Honglei Ji, Yi Tan, Lu Cai
AIMS: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by sulforaphane (SFN) protects from, and deletion of the Nrf2 gene exaggerates, diabetic cardiomyopathy. Angiotensin II (Ang II) plays a critical role in the development of diabetic cardiomyopathy. Therefore, whether SFN prevents Ang II-induced cardiomyopathy through activation of Nrf2 was examined using wild-type, global deletion of Nrf2 gene (Nrf2-KO) and cardiomyocyte-specific overexpression of Nrf2 gene (Nrf2-TG) mice...
January 2, 2018: Redox Biology
https://www.readbyqxmd.com/read/29316264/heme-oxygenase-1-affects-generation-and-spontaneous-cardiac-differentiation-of-induced-pluripotent-stem-cells
#6
Jacek Stepniewski, Tomasz Pacholczak, Aniela Skrzypczyk, Maciej Ciesla, Agata Szade, Krzysztof Szade, Romain Bidanel, Agnieszka Langrzyk, Radoslaw Grochowski, Felix Vandermeeren, Neli Kachamakova-Trojanowska, Mateusz Jez, Grazyna Drabik, Mahito Nakanishi, Alicja Jozkowicz, Jozef Dulak
Cellular stress can influence efficiency of iPSCs generation and their differentiation. However, the role of intracellular cytoprotective factors in these processes is still not well known. Therefore, we investigated the effect of HO-1 (Hmox1) or Nrf2 (Nfe2l2), two major cytoprotective genes. Hmox1-/- fibroblasts demonstrated decreased reprogramming efficiency in comparison to Hmox1+/+ cells. Reversely, pharmacological enhancement of HO-1 resulted in higher number of iPSCs colonies. Importantly, elevated level of both p53 and p53-regulated miR-34a and 14-3-3σ was observed in HO-1-deficient fibroblasts whereas downregulation of p53 in these cells markedly increased their reprogramming efficiency...
January 9, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29277538/sexual-dimorphism-in-response-to-a-nrf2-inducer-in-a-model-for-pachyonychia-congenita
#7
Michelle L Kerns, Jill M C Hakim, Abigail Zieman, Rosemary G Lu, Pierre A Coulombe
Sex is an influential factor regarding pathophysiology and therapeutic response in human disease. Pachyonychia congenita (PC) is caused by mutations in keratin genes and typified by dystrophic lesions affecting nails, glands, oral mucosa, and palmar-plantar epidermis. Painful palmar-plantar keratoderma (PPK) severely impair mobility in PC. Mice genetically null for keratin 16 (Krt16), one of the genes mutated in PC, develop PC-like PPK. In male Krt16-/- mice, oxidative stress associated with impaired glutathione synthesis and NRF2-dependent gene expression precedes PPK onset, which can be prevented by topical sulforaphane (SF)-mediated activation of NRF2 (Kerns et al...
December 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29242678/keap1-and-done-targeting-the-nrf2-pathway-with-sulforaphane
#8
Albena T Dinkova-Kostova, Jed W Fahey, Rumen V Kostov, Thomas W Kensler
Background: Since the re-discovery of sulforaphane in 1992 and the recognition of the bioactivity of this phytochemical, many studies have examined its mode of action in cells, animals and humans. Broccoli, especially as young sprouts, is a rich source of sulforaphane and broccoli-based preparations are now used in clinical studies probing efficacy in health preservation and disease mitigation. Many putative cellular targets are affected by sulforaphane although only one, KEAP1-NRF2 signaling, can be considered a validated target at this time...
November 2017: Trends in Food Science & Technology
https://www.readbyqxmd.com/read/29241671/mkp-1-protects-mice-against-toxin-induced-liver-damage-by-promoting-the-nrf2-cytoprotective-response
#9
Lin Luo, Yeru Chen, Hongyan Wang, Shengcun Wang, Kaihua Liu, Xin Li, Xiu Jun Wang, Xiuwen Tang
The present study was undertaken to investigate the possible protective effect of mitogen-activated protein kinase phosphatase 1 (Mkp-1) on toxin-induced hepatic injury. Here, we uncovered a positive feedback loop between Mkp-1, a dual threonine/tyrosine phosphatase, and nuclear factor erythroid 2-related factor 2 (Nrf2), a crucial regulator of the defense system in the liver. Mkp-1-/- mice exhibited decreased protein levels of Nrf2, phase II gene products, and reduced glutathione (GSH) in the liver. Induction of detoxifying enzymes by the Nrf2 activator butylated hydroxyanisole (BHA) or sulforaphane, was attenuated in the liver and small intestines of Mkp-1-/- mice, indicating that the Nrf2 signaling pathway is impaired as a result of Mkp-1 deficiency...
December 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#10
Wenji Li, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, RenYi Wu, Linbo Gao, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydrothiopyran-4-one (F10) and (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways...
December 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29224018/sulforaphane-treatment-of-stress-urinary-incontinence-via-the-nrf2-are-pathway-in-a-rat-model
#11
Xiang Wan, Chong Liu, Yan-Bo Chen, Meng Gu, Zhi-Kang Cai, Qi Chen, Zhong Wang
BACKGROUND/AIMS: To explore the effect of sulforaphane (SFN) treatment in rats through the induction of Stress Urinary Incontinence (SUI) via the Nrf2-ARE pathway. METHODS: A total of 18 female rats (Sprague-Dawley) were assigned to three groups: a control group, an SUI group, and an SUI+SFN group (six rats per group). Rats in the treatment groups were induced via postpartum vaginal balloon dilation and bilateral ovariectomy. Rats in the SUI+SFN group were treated via intraperitoneal injection once per day for a total of one month...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29205354/podocytes-are-new-cellular-targets-of-haemoglobin-mediated-renal-damage
#12
Alfonso Rubio-Navarro, Maria Dolores Sanchez-Niño, Melania Guerrero-Hue, Cristina García-Caballero, Eduardo Gutiérrez, Claudia Yuste, Ángel Sevillano, Manuel Praga, Javier Egea, Elena Román, Pablo Cannata, Rosa Ortega, Isabel Cortegano, Belén de Andrés, María Luisa Gaspar, Susana Cadenas, Alberto Ortiz, Jesús Egido, Juan Antonio Moreno
Recurrent and massive intravascular haemolysis induces proteinuria, glomerulosclerosis, and progressive impairment of renal function, suggesting podocyte injury. However, the effects of haemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway, and altered podocyte morphology, with decreased expression of the slit diaphragm proteins nephrin and synaptopodin...
December 4, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29154837/neuroprotective-effect-of-an-nrf2-are-activator-identified-from-a-chemical-library-on-dopaminergic-neurons
#13
Yasuhiko Izumi, Harue Kataoka, Yuri Inose, Akinori Akaike, Yutaka Koyama, Toshiaki Kume
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is a possible therapeutic target for treating diseases related to oxidative stress. Nrf2 activators often exhibit cytotoxicity due to nonspecific electrophilic reactions with thiol groups. We screened a chemical library to explore Nrf2 activators with a wide safety margin. In at least in vitro experiments, TPNA10168, identified from the library, showed a higher efficacy in Nrf2 activation and a lower cytotoxicity than sulforaphane, a well-known Nrf2 activator...
January 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29143802/the-inhibitory-effects-of-cobalt-protoporphyrin-ix-and-cannabinoid-2-receptor-agonists-in-type-2-diabetic-mice
#14
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/29137315/protective-effects-of-sulforaphane-on-di-n-butylphthalate-induced-testicular-oxidative-stress-injury-in-male-mice-offsprings-via-activating-nrf2-are-pathway
#15
Zhiqiang Qin, Jingyuan Tang, Peng Han, Xuping Jiang, Chengdi Yang, Ran Li, Min Tang, Baixin Shen, Wei Wang, Chao Qin, Wei Zhang
Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111554/sulforaphane-protects-mle-12-lung-epithelial-cells-against-oxidative-damage-caused-by-ambient-air-particulate-matter
#16
An-Shi Wang, Yan Xu, Zhuang-Wei Zhang, Bei-Bei Lu, Xuan Yin, An-Jun Yao, Li-Yuan Han, Zu-Quan Zou, Zhen Li, Xiao-Hong Zhang
Ambient air particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) can cause pulmonary injury. Oxidative stress is thought to be an important mechanism of PM2.5-mediated toxicity. Sulforaphane (SFN), a compound derived from cruciferous vegetables, is a well-known potent antioxidant; however, its protective effect on lung epithelial cells exposed to PM2.5 is unclear. The results showed that SFN pre-treatment markedly inhibited PM2.5-induced apoptosis of the type II alveolar epithelial cell line MLE-12 by elevating glutathione S-transferase levels and decreasing reactive oxygen species...
November 7, 2017: Food & Function
https://www.readbyqxmd.com/read/29096318/sulforaphane-attenuates-postnatal-proteasome-inhibition-and-improves-spatial-learning-in-adult-mice
#17
Aditya Sunkaria, Supriya Bhardwaj, Aarti Yadav, Avishek Halder, Rajat Sandhir
Proteasomes are known to degrade proteins involved in various processes like metabolism, signal transduction, cell-cycle regulation, inflammation, and apoptosis. Evidence showed that protein degradation has a strong influence on developing neurons as well as synaptic plasticity. Here, we have shown that sulforaphane (SFN) could prevent the deleterious effects of postnatal proteasomal inhibition on spatial reference and working memory of adult mice. One day old Balb/c mice received intracerebroventricular injections of MG132 and SFN...
October 4, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29074861/sulforaphane-reactivates-cellular-antioxidant-defense-by-inducing-nrf2-are-prdx6-activity-during-aging-and-oxidative-stress
#18
Eri Kubo, Bhavana Chhunchha, Prerna Singh, Hiroshi Sasaki, Dhirendra P Singh
Upon oxidative stress and aging, Nrf2 (NFE2-related factor2) triggers antioxidant defense genes to defends against homeostatic failure. Using human(h) or rat(r) lens epithelial cells (LECs) and aging human lenses, we showed that a progressive increase in oxidative load during aging was linked to a decline in Prdx6 expression. DNA binding experiments using gel-shift and ChIP assays demonstrated a progressive reduction in Nrf2/ARE binding (-357/-349) of Prdx6 promoter. The promoter (-918) with ARE showed a marked reduction in young vs aged hLECs, which was directly correlated to decreased Nrf2/ARE binding...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29057804/nrf2-inducers-counteract-neurodegeneration-in-frataxin-silenced-motor-neurons-disclosing-new-therapeutic-targets-for-friedreich-s-ataxia
#19
Sara Petrillo, Emanuela Piermarini, Anna Pastore, Gessica Vasco, Tommaso Schirinzi, Rosalba Carrozzo, Enrico Bertini, Fiorella Piemonte
Oxidative stress is actively involved in Friedreich's Ataxia (FA), thus pharmacological targeting of the antioxidant machinery may have therapeutic value. Here, we analyzed the relevance of the antioxidant phase II response mediated by the transcription factor Nrf2 on frataxin-deficient cultured motor neurons and on fibroblasts of patients. The in vitro treatment of the potent Nrf2 activator sulforaphane increased Nrf2 protein levels and led to the upregulation of phase II antioxidant enzymes. The neuroprotective effects were accompanied by an increase in neurites' number and extension...
October 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29018242/nuclear-factor-erythroid-derived-2-like-2-activation-increases-exercise-endurance-capacity-via-redox-modulation-in-skeletal-muscles
#20
Sechang Oh, Shoichi Komine, Eiji Warabi, Kentaro Akiyama, Akiko Ishii, Kazunori Ishige, Yuji Mizokami, Keisuke Kuga, Masaki Horie, Yoshihiro Miwa, Takao Iwawaki, Masayuki Yamamoto, Junichi Shoda
Sulforaphane (SFN) plays an important role in preventing oxidative stress by activating the nuclear factor (erythroid derived 2)-like 2 (Nrf2) signalling pathway. SFN may improve exercise endurance capacity by counteracting oxidative stress-induced damage during exercise. We assessed running ability based on an exhaustive treadmill test (progressive-continuous all-out) and examined the expression of markers for oxidative stress and muscle damage. Twelve- to 13-week-old Male wild-type mice (Nrf2 (+/+)) and Nrf2-null mice (Nrf2 (-/-)) on C57BL/6J background were intraperitoneally injected with SFN or vehicle prior to the test...
October 10, 2017: Scientific Reports
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