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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#1
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
#2
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-hemoglobin-mediated-renal-damage
#3
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 hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. However, the effects of hemoglobin (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 expressionof 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
#4
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...
November 14, 2017: 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28976703/the-effects-of-nrf2-modulation-on-the-initiation-and-progression-of-chemically-and-genetically-induced-lung-cancer
#12
Shasha Tao, Montserrat Rojo de la Vega, Eli Chapman, Aikseng Ooi, Donna D Zhang
Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations...
October 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28947488/treatment-with-sulforaphane-produces-antinociception-and-improves-morphine-effects-during-inflammatory-pain-in-mice
#13
Alejandro Redondo, Pablo Aníbal Ferreira Chamorro, Gabriela Riego, Sergi Leánez, Olga Pol
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ-opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain...
December 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28901514/multimodal-actions-of-the-phytochemical-sulforaphane-suppress-both-ar-and-ar-v7-in-22rv1-cells-advocating-a-potent-pharmaceutical-combination-against-castration-resistant-prostate-cancer
#14
Namrata Khurana, Hogyoung Kim, Partha K Chandra, Sudha Talwar, Pankaj Sharma, Asim B Abdel-Mageed, Suresh C Sikka, Debasis Mondal
Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1)...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28888052/mir-21-mediated-suppression-of-smad7-induces-tgf%C3%AE-1-and-can-be-inhibited-by-activation-of-nrf2-in-alcohol-treated-lung-fibroblasts
#15
Lucian T Marts, David E Green, Stephen T Mills, Tamara Murphy, Viranuj Sueblinvong
BACKGROUND: We previously demonstrated that chronic alcohol ingestion augments TGFβ1 expression in the lung fibroblast and increases the risk of fibroproliferative disrepair in a mouse model of acute lung injury. The effect of alcohol on TGFβ1 is mitigated by treatment with sulforaphane (SFP), which can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, the mechanisms by which alcohol amplifies, or SFP attenuates, TGFβ1 expression in the fibroblast are not known...
November 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28871145/reversible-keap1-inhibitors-are-preferential-pharmacological-tools-to-modulate-cellular-mitophagy
#16
Nikolaos D Georgakopoulos, Michele Frison, Maria Soledad Alvarez, Hélène Bertrand, Geoff Wells, Michelangelo Campanella
Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28863281/aging-related-decline-in-the-induction-of-nrf2-regulated-antioxidant-genes-in-human-bronchial-epithelial-cells
#17
Lulu Zhou, Hongqiao Zhang, Kelvin J A Davies, Henry Jay Forman
Evidence from animal studies suggests that stress-induced increases in Nrf2-regulated antioxidant gene expression, a critical mechanism of cellular protection, declines with aging. This study examined whether this also occurs in humans. We measured the basal and inducible levels of Nrf2-regulated antioxidant genes in human bronchial epithelial (HBE) cells from subjects of young adult (21-29 years) and older (60-69 years) non-smokers, and explored factors affecting expresion. The basal expression of three representative Nrf2-regulated genes, the catalytic and modulator subunits of glutamate cysteine ligase (GCLC and GCLM, respectively), and NAD(P)H quinone oxidoreductase 1 (NQO1), was higher in cells from the older donors compared with cells from the young adult donors...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28790194/characterization-of-the-potent-selective-nrf2-activator-3-pyridin-3-ylsulfonyl-5-trifluoromethyl-2h-chromen-2-one-in-cellular-and-in-vivo-models-of-pulmonary-oxidative-stress
#18
John G Yonchuk, Joseph P Foley, Brian J Bolognese, Gregory Logan, William E Wixted, Jen-Pyng Kou, Diana G Chalupowicz, Heidi G Feldser, Yolanda Sanchez, Hong Nie, James F Callahan, Jeffrey K Kerns, Patricia L Podolin
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key regulator of oxidative stress and cellular repair and can be activated through inhibition of its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (Keap1). Several small molecule disrupters of the Nrf2-Keap1 complex have recently been tested and/or approved for human therapeutic use but lack either potency or selectivity. The main goal of our work was to develop a potent, selective activator of NRF2 as protection against oxidative stress. In human bronchial epithelial cells, our Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one (PSTC), induced Nrf2 nuclear translocation, Nrf2-regulated gene expression, and downstream signaling events, including induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme activity and heme oxygenase-1 protein expression, in an Nrf2-dependent manner...
October 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28768661/all-trans-retinoic-acid-mediated-cytoprotection-in-renal-epithelial-cells-is-coupled-to-p-erk-activation-in-a-ros-independent-manner
#19
Jessica M Sapiro, Terrence J Monks, Serrine S Lau
Although all-trans-retinoic acid (ATRA) provides protection against a variety of conditions in vivo, particularly ischemia, the molecular mechanisms underpinning these effects remain unclear. The present studies were designed to assess potential mechanisms by which ATRA affords cytoprotection against renal toxicants in LLC-PK1 cells. Pretreatment of LLC-PK1 cells with ATRA (25 μM) for 24 hr afforded cytoprotection against oncotic cell death induced by p-aminophenol (PAP), 2-(glutathion-S-yl)hydroquinone (MGHQ), and iodoacetamide but not against apoptotic cell death induced by cisplatin...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28730528/sulforaphane-promotes-mitochondrial-protection-in-sh-sy5y-cells-exposed-to-hydrogen-peroxide-by-an-nrf2-dependent-mechanism
#20
Marcos Roberto de Oliveira, Flávia de Bittencourt Brasil, Cristina Ribas Fürstenau
Sulforaphane (SFN; C6H11NOS2) is an isothiocyanate found in cruciferous vegetables, such as broccoli, kale, and radish. SFN exhibits antioxidant, anti-apoptotic, anti-tumor, and anti-inflammatory activities in different cell types. However, it was not previously demonstrated whether and how this natural compound would exert mitochondrial protection experimentally. Therefore, we investigated here the effects of a pretreatment (for 30 min) with SFN at 5 μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) at 300 μM for 24 h...
July 20, 2017: Molecular Neurobiology
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