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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/28730528/sulforaphane-promotes-mitochondrial-protection-in-sh-sy5y-cells-exposed-to-hydrogen-peroxide-by-an-nrf2-dependent-mechanism
#1
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
https://www.readbyqxmd.com/read/28710020/nrf2-deficiency-exacerbates-ochratoxin-a-induced-toxicity-in-vitro-and-in-vivo
#2
Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, Paulina Podkalicka, Olga Mucha, Alicja Jozkowicz, Jozef Dulak
Several mechanisms are postulated to be responsible for nephrotoxic and nephrocarcinogenic activities of mycotoxin and food contaminant, ochratoxin A (OTA). Although Nrf2 transcription factor was suggested to be involved in OTA-mediated renal injury, comprehensive study evaluating the effect of OTA toxicity in Nrf2 knock-out mice with special regard to sex-dependency has not been performed yet. Our results clearly show exacerbated OTA toxicity in porcine tubular epithelial cells after shRNA-mediated Nrf2 inhibition as well as in proximal tubular cells isolated from Nrf2(-/-) male mice in comparison to cells derived from their wild-type counterparts...
July 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28700700/the-induction-of-the-transcription-factor-nrf2-enhances-the-antinociceptive-effects-of-delta-opioid-receptors-in-diabetic-mice
#3
Christina McDonnell, Sergi Leánez, Olga Pol
The involvement of heme oxygenase 1 (HO-1) in the modulation of the antinociceptive effects of opioids in type 1 diabetes has been demonstrated but the role played by the transcription factor Nrf2 in the regulation of painful neuropathy and in the effects and expression of δ-opioid receptors (DOR) in type 2 diabetes, has not been studied. In male BKS.Cg-m+/+Leprdb/J (db/db) mice, the anti-allodynic effects produced by a Nrf2 transcription factor activator, sulforaphane (SFN) administered alone and combined with two DOR agonists, [d-Pen(2),d-Pen(5)]-Enkephalin (DPDPE) and (+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N diethylbenzamide (SNC-80), were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28636290/sulforaphane-protection-against-the-development-of-doxorubicin-induced-chronic-heart-failure-is-associated-with-nrf2-upregulation
#4
Yang Bai, Qiang Chen, Yun-Peng Sun, Xuan Wang, Li Lv, Li-Ping Zhang, Jin-Sha Liu, Song Zhao, Xiao-Lu Wang
Doxorubicin (DOX) is an anthracycline anti-tumor drug. However, its clinical use is limited by dose-dependent cardiotoxicity, and even progresses to chronic heart failure (CHF). OBJECTIVE: This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX-induced CHF. METHODS: Male Sprague Dawley rats who received treatment for six weeks were divided into four groups (n=30 per group): control, SFN, DOX, and DOX plus SFN group. RESULTS: Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28615356/sulforaphane-reduces-hepatic-glucose-production-and-improves-glucose-control-in-patients-with-type-2-diabetes
#5
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M J Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, Anders H Rosengren
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28607561/the-transcription-factor-nrf2-protects-angiogenic-capacity-of-endothelial-colony-forming-cells-in-high-oxygen-radical-stress-conditions
#6
Hendrik Gremmels, Olivier G de Jong, Diënty H Hazenbrink, Joost O Fledderus, Marianne C Verhaar
BACKGROUND: Endothelial colony forming cells (ECFCs) have shown a promise in tissue engineering of vascular constructs, where they act as endothelial progenitor cells. After implantation, ECFCs are likely to be subjected to elevated reactive oxygen species (ROS). The transcription factor Nrf2 regulates the expression of antioxidant enzymes in response to ROS. METHODS: Stable knockdown of Nrf2 and Keap1 was achieved by transduction with lentiviral shRNAs; activation of Nrf2 was induced by incubation with sulforaphane (SFN)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28587109/identification-of-non-electrophilic-nrf2-activators-from-approved-drugs
#7
Qing-Ye Zhang, Xin-Yi Chu, Ling-Han Jiang, Meng-Yuan Liu, Zhi-Ling Mei, Hong-Yu Zhang
Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to prevent or lower the risk of oxidative stress-related diseases. Until now, most research has focused on electrophilic indirect Nrf2 activators, but the risk of 'off-target' effects may be associated with these activators. To find novel small non-electrophilic modulators of Nrf2, we started from chemical agents derived from a connectivity map (cMap) and identified 22 non-electrophilic potential Nrf2-activating drugs through a drug repositioning tactic...
May 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28586068/sulforaphane-increases-nrf2-expression-and-protects-alveolar-epithelial-cells-against-injury-caused-by-cigarette-smoke-extract
#8
Zongxian Jiao, Jiachen Chang, Jing Li, Dengmei Nie, Huijuan Cui, Dongfang Guo
Cigarette smoking is a primary risk factor for chronic obstructive pulmonary disease (COPD), as it damages epithelial cells through a variety of mechanisms. Sulforaphane (SFN) is an antioxidant agent, which exerts protective effects against cell damage by activating the nuclear factor erythroid 2 like 2 (NFE2L2; Nrf2). The present study was undertaken to investigate the effects and underlying mechanisms of SFN in preventing cigarette smoke extract (CSE)‑induced oxidative damage to RLE‑6TN rat lung epithelial cells...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28583601/concentration-dependent-antioxidative-and-apoptotic-effects-of-sulforaphane-on-bovine-granulosa-cells-in%C3%A2-vitro
#9
Md Mahmodul Hasan Sohel, Yusuf Konca, Bilal Akyuz, Korhan Arslan, Serpil Sariozkan, Mehmet Ulas Cinar
Sulforaphane (SFN) has received a great deal of research attention because of its ability to induce the production of a battery of antioxidant enzymes in certain concentrations through the activation of the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, which may effectively neutralize reactive oxygen species (ROS) induced oxidative stress. This study was conducted to investigate the potential of different concentrations of SFN in inducing antioxidative and apoptotic effects in granulosa cells (GCs)...
July 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/28572033/blood-brain-barrier-disruption-in-diabetic-mice-is-linked-to-nrf2-signaling-deficits-role-of-abcb10
#10
Ravi K Sajja, Shikha Prasad, Suni Tang, Mohammad A Kaisar, Luca Cucullo
Blood-brain barrier (BBB) damage is a critical neurovascular complication of diabetes mellitus that adversely affects the CNS health and function. Previously, we showed the protective role of NF-E2 related factor-2 (Nrf2), a redox sensitive transcription factor, in regulation of BBB integrity. Given the pathogenic role of mitochondrial oxidative stress in diabetes-related microvascular complications, we focused on assessing: 1) the impact of diabetes on brain Nrf2 in correlation with BBB permeability and 2) Nrf2-dependent regulation of the mitochondrial transporter ABCB10, an essential player in mitochondrial function and redox balance at BBB endothelium...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28550120/hiv-1-decreases-nrf2-are-activity-and-phagocytic-function-in-alveolar-macrophages
#11
Bashar S Staitieh, Lingmei Ding, Wendy A Neveu, Paul Spearman, David M Guidot, Xian Fan
Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#12
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28515158/anti-psoriatic-drug-monomethylfumarate-increases-nuclear-factor-erythroid-2-related-factor-2-levels-and-induces-aquaporin-3-mrna-and-protein-expression
#13
Inas Helwa, Vivek Choudhary, Xunsheng Chen, Ismail Kaddour-Djebbar, Wendy B Bollag
Oxidative stress contributes to inflammatory skin diseases, including psoriasis. Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular antioxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses...
August 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28487960/sulforaphane-prevents-bleomycin%C3%A2-induced-pulmonary-fibrosis-in-mice-by-inhibiting-oxidative-stress-via-nuclear-factor-erythroid-2%C3%A2-related-factor%C3%A2-2-activation
#14
Bingdi Yan, Zhongsen Ma, Shaomin Shi, Yuxin Hu, Tiangang Ma, Gao Rong, Junling Yang
Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2‑related factor‑2 (Nrf2) prevents damage to cells from oxidative stress by regulating the expression of antioxidant proteins. Sulforaphane (SFN), an Nrf2 activator, additionally regulates excessive oxidative stress by promoting the expression of endogenous antioxidants. The present study investigated if SFN protects against lung injury induced by bleomycin (BLM). The secondary aim of the present study was to assess if this protection mechanism involves upregulation of Nrf2 and its downstream antioxidants...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28412310/increased-seizure-susceptibility-and-other-toxicity-symptoms-following-acute-sulforaphane-treatment-in-mice
#15
Katarzyna Socała, Dorota Nieoczym, Edyta Kowalczuk-Vasilev, Elżbieta Wyska, Piotr Wlaź
Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice...
July 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28408365/immunomodulators-targeting-marco-expression-improve-resistance-to-postinfluenza-bacterial-pneumonia
#16
Muzo Wu, John G Gibbons, Glen M DeLoid, Alice S Bedugnis, Rajesh K Thimmulappa, Shyam Biswal, Lester Kobzik
Downregulation of the alveolar macrophage (AM) receptor with collagenous structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a major cause of morbidity and mortality. We sought to determine whether immunomodulation of MARCO could improve host defense and resistance to secondary bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO expression between days 9 and 11 after influenza infection and indicated important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM-like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated with IFNγ to model influenza effects...
July 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28389405/delayed-nrf2-regulated-antioxidant-gene-induction-in-response-to-silica-nanoparticles
#17
Hongqiao Zhang, Lulu Zhou, Jenay Yuen, Nancy Birkner, Valerie Leppert, Peggy A O'Day, Henry Jay Forman
Silica nanoparticles with iron on their surface cause the production of oxidants and stimulate an inflammatory response in macrophages. Nuclear factor erythroid-derived 2 - like factor 2 (Nrf2) signaling and its regulated antioxidant genes play critical roles in maintaining redox homeostasis. In this study we investigated the regulation of four representative Nrf2-regulated antioxidant genes; i.e., glutamate cysteine ligase (GCL) catalytic subunit (GCLC), GCL modifier subunit (GCLM), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1), by iron-coated silica nanoparticles (SiO2-Fe) in human THP-1 macrophages...
July 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28386307/sulforaphane-protects-against-high-cholesterol-induced-mitochondrial-bioenergetics-impairments-inflammation-and-oxidative-stress-and-preserves-pancreatic-%C3%AE-cells-function
#18
Catalina Carrasco-Pozo, Kah Ni Tan, Martin Gotteland, Karin Borges
Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28350841/correction-lack-of-effect-of-oral-sulforaphane-administration-on-nrf2-expression-in-copd-a-randomized-double-blind-placebo-controlled-trial
#19
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
[This corrects the article DOI: 10.1371/journal.pone.0163716.].
2017: PloS One
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
#20
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
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