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Nrf2 AND sulforaphane

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https://www.readbyqxmd.com/read/29684505/protective-effects-of-sulforaphane-on-cognitive-impairments-and-ad-like-lesions-in-diabetic-mice-are-associated-with-the-upregulation-of-nrf2-transcription-activity
#1
Die Pu, Yuxing Zhao, Jinliang Chen, Yue Sun, Ankang Lv, Shiyu Zhu, Cheng Luo, Kexiang Zhao, Qian Xiao
Type 2 diabetes mellitus (T2DM)-associated oxidative stress contributes to cognitive deficiencies and Alzheimer's disease (AD). Sulforaphane (SFN) is a pharmacological activator of Nrf2 that provokes Nrf2-mediated intracellular defenses, including antioxidant and anti-inflammatory responses, under oxidative stress (OS) conditions. This study investigated the effects of SFN on DM-related cognitive decline and its potential mechanisms. Morris water maze (MWM) tests showed that SFN (1 mg/kg i.p. for 28 days) mitigated the cognitive decline of db/db mice, a transgenic mouse model of T2DM...
April 20, 2018: Neuroscience
https://www.readbyqxmd.com/read/29618945/inducers-of-senescence-toxic-compounds-and-senolytics-the-multiple-faces-of-nrf2-activating-phytochemicals-in-cancer-adjuvant-therapy
#2
REVIEW
Marco Malavolta, Massimo Bracci, Lory Santarelli, Md Abu Sayeed, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza, Andrea Basso, Maurizio Cardelli, Mauro Provinciali
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29565500/expression-of-nrf2-keap1-are-signal-pathway-in-traumatic-lung-injury-and-functional-study
#3
L-Y Hu, J-B Cui, X-M Xu, Z-H Huang, H-T Jiao
OBJECTIVE: Traumatic lung injury (TLI) can cause inflammation and oxidative stress, or even leads to acute respiratory distress syndrome (ARDS) and death. Nuclear factor erythroid-2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signal pathway participates in disease occurrence and progression via regulating inflammatory and oxidative stress response, but with its expression and functional roles in TLI largely unknown. MATERIALS AND METHODS: Wistar rats were randomly divided into control group, TLI group by crushing method, and Nrf2 activation group which received Nrf2 specific agonist sulforaphane 30 min before TLI treatment...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29547002/opsonic-phagocytosis-in-chronic-obstructive-pulmonary-disease-is-enhanced-by-nrf2-agonists
#4
Martin A Bewley, Richard C Budd, Eilise Ryan, Joby Cole, Paul Collini, Jennifer Marshall, Umme Kolsum, Gussie Beech, Richard D Emes, Irina Tcherniaeva, Guy A M Berbers, Sarah R Walmsley, Gavin Donaldson, Jadwiga A Wedzicha, Iain Kilty, William Rumsey, Yolanda Sanchez, Christopher E Brightling, Louise E Donnelly, Peter J Barnes, Dave Singh, Moira K B Whyte, David H Dockrell
RATIONALE: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined. OBJECTIVES: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences and potential for therapeutic manipulation of these defects. METHODS: We isolated alveolar macrophages (AM) and monocyte-derived macrophages (MDM) from a cohort of COPD patients and controls within the MRC COPD-MAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features...
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29533123/protective-effects-of-sulforaphane-in-experimental-vascular-cognitive-impairment-contribution-of-the-nrf2-pathway
#5
Leilei Mao, Tuo Yang, Xin Li, Xia Lei, Yang Sun, Yongfang Zhao, Wenting Zhang, Yanqin Gao, Baoliang Sun, Feng Zhang
The major pathophysiological process of vascular cognitive impairment (VCI) is chronic cerebral ischemia, which causes disintegration of the blood-brain barrier (BBB), neuronal death, and white matter injury. This study aims to test whether sulforaphane (Sfn), a natural activator of nuclear factor erythroid 2-related factor 2 (Nrf2), reduces the chronic ischemic injury and cognitive dysfunction after VCI. Experimental VCI was induced in rats by permanent occlusion of both common carotid arteries for six weeks...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29530794/nrf2-inhibits-oxaliplatin-induced-peripheral-neuropathy-via-protection-of-mitochondrial-function
#6
Yang Yang, Lan Luo, Xueting Cai, Yuan Fang, Jiaqi Wang, Gang Chen, Jie Yang, Qian Zhou, Xiaoyan Sun, Xiaolan Cheng, Huaijiang Yan, Wuguang Lu, Chunping Hu, Peng Cao
Oxaliplatin-induced peripheral neuropathy (OIPN) is a severe, dose-limiting toxicity associated with cancer chemotherapy. The efficacy of antioxidant administration in OIPN is debatable, as the promising preliminary results obtained with a number of antioxidants have not been confirmed in larger clinical trials. Besides its antioxidant activity, the transcription factor, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2 (Nrf2) plays a crucial role in the maintenance of mitochondrial homeostasis, and mitochondrial dysfunction is a key contributor to OIPN...
March 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29518137/sulforaphane-potentiates-anticancer-effects-of-doxorubicin-and-attenuates-its-cardiotoxicity-in-a-breast-cancer-model
#7
Chhanda Bose, Sanjay Awasthi, Rajendra Sharma, Helen Beneš, Martin Hauer-Jensen, Marjan Boerma, Sharda P Singh
Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known...
2018: PloS One
https://www.readbyqxmd.com/read/29507103/transcription-factor-nrf2-as-a-therapeutic-target-for-chronic-diseases-a-systems-medicine-approach
#8
REVIEW
Antonio Cuadrado, Gina Manda, Ahmed Hassan, María José Alcaraz, Coral Barbas, Andreas Daiber, Pietro Ghezzi, Rafael León, Manuela G López, Baldo Oliva, Marta Pajares, Ana I Rojo, Natalia Robledinos-Antón, Angela M Valverde, Emre Guney, Harald H H W Schmidt
Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome)...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29473125/sulforaphane-attenuated-the-pro-inflammatory-state-induced-by-hydrogen-peroxide-in-sh-sy5y-cells-through-the-nrf2-ho-1-signaling-pathway
#9
Marcos Roberto de Oliveira, Flávia Bittencourt Brasil, Cristina Ribas Fürstenau
Sulforaphane (SFN), an isothiocyanate obtained from cruciferous vegetables, exerts antioxidant, antiapoptotic, and antitumor activities in different cell types. Moreover, SFN has been viewed as an anti-inflammatory agent. Nonetheless, the mechanism underlying the ability of SFN in modulating the immune response in mammalian cells is not completely understood yet. Therefore, we investigated here whether and how SFN would be effective in preventing inflammation induced by a pro-oxidant agent (hydrogen peroxide, H2 O2 ) in the human neuroblastoma SH-SY5Y cells...
February 23, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29472449/nrf2-activation-attenuates-genetic-endoplasmic-reticulum-stress-induced-by-a-mutation-in-the-phosphomannomutase-2-gene-in-zebrafish
#10
Katsuki Mukaigasa, Tadayuki Tsujita, Vu Thanh Nguyen, Li Li, Hirokazu Yagi, Yuji Fuse, Yaeko Nakajima-Takagi, Koichi Kato, Masayuki Yamamoto, Makoto Kobayashi
Nrf2 plays critical roles in animals' defense against electrophiles and oxidative stress by orchestrating the induction of cytoprotective genes. We previously isolated the zebrafish mutant it768 , which displays up-regulated expression of Nrf2 target genes in an uninduced state. In this paper, we determine that the gene responsible for it768 was the zebrafish homolog of phosphomannomutase 2 (Pmm2), which is a key enzyme in the initial steps of N-glycosylation, and its mutation in humans leads to PMM2-CDG (congenital disorders of glycosylation), the most frequent type of CDG...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29466800/the-association-between-oxidative-stress-alleviation-via-sulforaphane-induced-nrf2-ho-1-nqo-1-signaling-pathway-activation-and-chronic-renal-allograft-dysfunction-improvement
#11
Daoyuan Lv, Qin Zhou, Yue Xia, Xu You, Zhihong Zhao, Yongqiang Li, Hequn Zou
BACKGROUND/AIMS: Chronic renal allograft dysfunction (CRAD) is a leading cause of long-term renal allograft loss. Oxidative stress may account for the nonspecific interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant intervention via Nrf2 signaling pathway activation might be a promising therapy for some kidney diseases. The present paper investigates whether there is an association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO-1/NQO-1 signaling pathway activation and CRAD improvement...
February 16, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29458173/deregulation-of-nrf2-are-signaling-pathway-causes-susceptibility-of-dystrophin-deficient-myotubes-to-menadione-induced-oxidative-stress
#12
Su Jin Choi, Hye Sun Kim
Duchenne muscular dystrophy (DMD) is an X chromosome-linked disorder caused by a mutation in the dystrophin gene. Many previous studies reported that the skeletal muscles of DMD patients were more susceptible to oxidative stress than those of healthy people. However, not much has been known about the responsible mechanism of the differential susceptibility. In this study, we established dystrophin knock-down (DysKD) cell lines by transfection of dystrophin shRNA lentiviral particles into C2 cells and found that DysKD myotubes are more vulnerable to menadione-induced oxidative stress than control myotubes...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29427794/concerted-redox-modulation-by-sulforaphane-alleviates-diabetes-and-cardiometabolic-syndrome
#13
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
#14
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
#15
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...
April 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29362432/nrf2-antioxidant-pathway-suppresses-numb-mediated-epithelial-mesenchymal-transition-during-pulmonary-fibrosis
#16
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
#17
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...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29316264/heme-oxygenase-1-affects-generation-and-spontaneous-cardiac-differentiation-of-induced-pluripotent-stem-cells
#18
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...
February 2018: IUBMB Life
https://www.readbyqxmd.com/read/29277538/sexual-dimorphism-in-response-to-an-nrf2-inducer-in-a-model-for-pachyonychia-congenita
#19
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 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 impairs mobility in pachyonychia congenita. Mice genetically null for keratin 16 (Krt16), one of the genes mutated in pachyonychia congenita, develop pachyonychia congenita-like PPK. In male Krt16-/- mice, oxidative stress associated with impaired glutathione synthesis and nuclear factor erythroid-derived 2 related factor 2 (NRF2)-dependent gene expression precedes PPK onset, which can be prevented by topical sulforaphane-mediated activation of NRF2...
December 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29242678/keap1-and-done-targeting-the-nrf2-pathway-with-sulforaphane
#20
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
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