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https://www.readbyqxmd.com/read/28088909/synergistic-interaction-between-heme-oxygenase-ho-and-nuclear-factor-e2-related-factor-2-nrf2-against-oxidative-stress-in-cardiovascular-related-diseases
#1
Joseph Fomusi Ndisang
BACKGROUND: Nuclear factor-erythroid related factor-2 (Nrf2) is a master regulator of transcriptional activation of anti-oxidants in cells. Similarly, heme oxygenase (HO) is a cytoprotective protein with anti-oxidant effects. This review article will shed more light on the interaction between Nrf2 and HO. METHODS AND RESULTS: A PubMed search was done for recent articles on Nrf2 and HO. These studies suggested that under normal physiological conditions, Nrf2 is bound within the cytoplasm to its repressor, Kelch-like ECH-associated protein (Keap1), an oxidative stress sensor...
January 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28073699/activation-of-nrf2-attenuates-carbonyl-stress-induced-by-methylglyoxal-in-human-neuroblastoma-cells-increase-in-gsh-levels-is-a-critical-event-for-the-detoxification-mechanism
#2
Shoichi Nishimoto, Shin Koike, Naho Inoue, Toshihiro Suzuki, Yuki Ogasawara
The present study focused on the methylglyoxal (MG) detoxification mechanism in neuroblastoma cells. The involvement of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway as a defense response against the formation of MG-modified proteins, which is well-known evidence of carbonyl stress, was also examined. We found that MG treatment resulted in accumulation of modified proteins bearing the structure of advanced glycation end products (AGEs) derived from MG in SH-SY5Y cells...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068647/berberine-an-isoquinoline-alkaloid-suppresses-txnip-mediated-nlrp3-inflammasome-activation-in-msu-crystal-stimulated-raw-264-7-macrophages-through-the-upregulation-of-nrf2-transcription-factor-and-alleviates-msu-crystal-induced-inflammation-in-rats
#3
Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264...
January 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28065782/4-hydroxynonenal-metabolites-and-adducts-in-pre-carcinogenic-conditions-and-cancer
#4
REVIEW
Françoise Guéraud
4-hydroxy-2-nonenal (HNE) is an amazing reactive compound, originating from lipid peroxidation within cells but also in food and considered as a "second messenger" of oxidative stress. Due to its chemical features, HNE is able to make covalent links with DNA, proteins and lipids. The aim of this review is to give a comprehensive summary of the chemical properties of HNE and of the consequences of its reactivity in relation to cancer development. The formation of exocyclic etheno-and propano-adducts and genotoxic effects are addressed...
January 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28065629/the-effects-of-emodin-on-cell-viability-respiratory-burst-and-gene-expression-of-nrf2-keap1-signaling-molecules-in-the-peripheral-blood-leukocytes-of-blunt-snout-bream-megalobrama-amblycephala
#5
Zhenxin Zhao, Jun Xie, Bo Liu, Xianping Ge, Changyou Song, Mingchun Ren, Qunlan Zhou, Linghong Miao, Huimin Zhang, Fan Shan, Zhenfei Yang
We determined the effects of emodin on the cell viability, respiratory burst activity, mRNA levels of antioxidative enzymes (Cu-Zn SOD, CAT and NOX2), and gene expressions of the Nrf2-Keap1 signaling molecules in the peripheral blood leukocytes of blunt snout bream. Triplicate groups of cultured cells were treated with different concentrations of emodin (0.04-25 μg/ml) for 24 h. Results showed that the emodin caused a dramatic loss in cell viability, and occurred in a dose-dependent manner. Emodin exposure (1-25 μg/ml) were significantly induced the ROS generation compared to the control...
January 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28061437/keap1-nrf2-pathway-in-kidney-cancer-frequent-methylation-of-keap1-gene-promoter-in-clear-renal-cell-carcinoma
#6
Federico Pio Fabrizio, Manuela Costantini, Massimiliano Copetti, Annamaria la Torre, Angelo Sparaneo, Andrea Fontana, Luana Poeta, Michele Gallucci, Steno Sentinelli, Paolo Graziano, Paola Parente, Vincenzo Pompeo, Laura De Salvo, Giuseppe Simone, Rocco Papalia, Francesco Picardo, Teresa Balsamo, Gerardo Paolo Flammia, Domenico Trombetta, Angela Pantalone, Klaas Kok, Ferronika Paranita, Lucia Anna Muscarella, Vito Michele Fazio
The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma)...
4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061435/mirna-141-attenuates-uv-induced-oxidative-stress-via-activating-keap1-nrf2-signaling-in-human-retinal-pigment-epithelium-cells-and-retinal-ganglion-cells
#7
Li-Bo Cheng, Ke-Ran Li, Nan Yi, Xiu-Miao Li, Feng Wang, Bo Xue, Ying-Shun Pan, Jin Yao, Qin Jiang, Zhi-Feng Wu
Activation of NF-E2-related factor 2 (Nrf2) signaling could protect cells from ultra violet (UV) radiation. We aim to provoke Nrf2 activation via downregulating its inhibitor Keap1 by microRNA-141 ("miR-141"). In both human retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs), forced-expression of miR-141 downregulated Keap1, causing Nrf2 stabilization, accumulation and nuclear translocation, which led to transcription of multiple antioxidant-responsive element (ARE) genes (HO1, NOQ1 and GCLC)...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28055010/continued-26s-proteasome-dysfunction-in-mouse-brain-cortical-neurons-impairs-autophagy-and-the-keap1-nrf2-oxidative-defence-pathway
#8
Aslihan Ugun-Klusek, Michael H Tatham, Jamal Elkharaz, Dumitru Constantin-Teodosiu, Karen Lawler, Hala Mohamed, Simon M L Paine, Glen Anderson, R John Mayer, James Lowe, E Ellen Billett, Lynn Bedford
The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pathomechanisms of neurodegenerative disease. Here we show that continued 26S proteasome dysfunction in mouse brain cortical neurons causes paranuclear accumulation of fragmented dysfunctional mitochondria, associated with earlier recruitment of Parkin and lysine 48-linked ubiquitination of mitochondrial outer membrane (MOM) proteins, including Mitofusin-2...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28042770/preventive-and-protective-roles-of-dietary-nrf2-activators-against-central-nervous-system-diseases
#9
Yang Sun, Tuo Yang, Rehana K Leak, Jun-He Chen, Feng Zhang
Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelch-like ECH associated protein 1, leading to Nrf2 inactivation via ubiquitination and degradation...
January 2, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28039084/halofuginone-enhances-the-chemo-sensitivity-of-cancer-cells-by-suppressing-nrf2-accumulation
#10
Kouhei Tsuchida, Tadayuki Tsujita, Makiko Hayashi, Asaka Ojima, Nadine Keleku-Lukwete, Fumiki Katsuoka, Akihito Otsuki, Haruhisa Kikuchi, Yoshiteru Oshima, Mikiko Suzuki, Masayuki Yamamoto
The KEAP1-NRF2 system regulates the cellular defence against oxidative and xenobiotic stresses. NRF2 is a transcription factor that activates the expression of cytoprotective genes encoding antioxidative, detoxifying and metabolic enzymes as well as transporters. Under normal conditions, KEAP1 represses NRF2 activity by degrading the NRF2 protein. When cells are exposed to stresses, KEAP1 stops promoting NRF2 degradation, and NRF2 rapidly accumulates and activates the transcription of target genes. Constitutive accumulation of NRF2 via a variety of mechanisms that disrupt KEAP1-mediated NRF2 degradation has been observed in various cancer types...
December 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28035409/morin-exerts-cytoprotective-effects-against-oxidative-stress-in-c2c12-myoblasts-via-the-upregulation-of-nrf2-dependent-ho-1-expression-and-the-activation-of-the-erk-pathway
#11
Moon Hee Lee, Min Ho Han, Dae-Sung Lee, Cheol Park, Su-Hyun Hong, Gi-Young Kim, Sang Hoon Hong, Kyoung Seob Song, Il-Whan Choi, Hee-Jae Cha, Yung Hyun Choi
In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and γH2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28033563/the-mitochondria-targeted-antioxidant-mitoq-ameliorated-tubular-injury-mediated-by-mitophagy-in-diabetic-kidney-disease-via-nrf2-pink1
#12
Li Xiao, Xiaoxuan Xu, Fan Zhang, Ming Wang, Yan Xu, Dan Tang, Jiahui Wang, Yan Qin, Yu Liu, Chengyuan Tang, Liyu He, Anna Greka, Zhiguang Zhou, Fuyou Liu, Zheng Dong, Lin Sun
Mitochondria play a crucial role in tubular injury in diabetic kidney disease (DKD). MitoQ is a mitochondria-targeted antioxidant that exerts protective effects in diabetic mice, but the mechanism underlying these effects is not clear. We demonstrated that mitochondrial abnormalities, such as defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression and mitochondrial fragmentation, occurred in the tubular cells of db/db mice, accompanied by reduced PINK and Parkin expression and increased apoptosis...
December 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/28025123/structured-dag-oil-ameliorates-renal-injury-in-streptozotocin-induced-diabetic-rats-through-inhibition-of-nf-%C3%AE%C2%BAb-and-activation-of-nrf2-pathway
#13
Kankana Das, Mahua Ghosh
Accumulating evidence suggested that inflammatory processes are involved in the development of diabetic nephropathy (DN). Here, we have tested the hypothesis that Caprylic Acid (Cy)-diacylglycerol (DAG) oil (Cy-DAG), a novel structurally formulated lipid with high nutritional value, ameliorated DN in streptozotocin (STZ)-induced diabetic rats through the anti-inflammatory mechanisms. Basic hematological, biochemical parameters, immunoblotting, immunofluorescence and flow cytometry analysis were performed to observe the anti-inflammatory potential of Cy-DAG oil...
December 24, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28024463/in-silico-evidence-for-binding-of-pentacyclic-triterpenoids-to-keap1-nrf2-protein-protein-binding-site
#14
Sarika M Kamble, Harun M Patel, Sameer N Goyal, Malleshappa N Noolvi, Umesh B Mahajan, Shreesh Ojha, Chandragouda R Patil
Kelch like ECH-associated protein 1 (Keap1) and Nuclear factor-E2 related factor 2 (Nrf2) binding is a key step in the ubiquitination and degradation of Nrf2. The compounds inhibiting this binding exert antioxidant actions. Naturally occurring pentacyclic triterpenoids (PTs) and their synthetic derivatives are projected as activators of Nrf2 signalling. The 16-mer Nrf2 peptide binding site on Keap-1 (PDB: 2 FLU) is proposed to be the prospective target for a tetracyclic triterpenoid called gedunine. In present study, seventy seven PTs of natural and synthetic origin are screened for Nrf2 stimulatory activity using online PASS (Prediction of Activity Spectrum of Substances) software followed by in-silico molecular docking against 16-mer Nrf2 peptide binding site on Keap-1...
December 14, 2016: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28012783/epigenetic-regulation-of-redox-signaling-in-diabetic-retinopathy-role-of-nrf2
#15
REVIEW
Renu A Kowluru, Manish Mishra
Diabetic retinopathy is a major vision threatening disease among working age adults, and increased oxidative stress is one of the prime causative factors in its pathogenesis. Increased reactive oxygen species (ROS) in the cytosol damage mitochondria, and due to compromised antioxidant signaling system and dysfunctional mitochondria with damaged mitochondrial DNA, ROS continue to pile up, accelerating capillary cell loss. In addition to other cellular and enzymatic defense systems, the retina is also equipped with the nuclear erythroid-2-p45-related factor-2 (Nrf2) antioxidant response element signaling pathway, which controls the expression of genes important in detoxification and elimination of ROS...
December 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28012440/nrf2-inhibition-reverses-the-resistance-of-cisplatin-resistant-head-and-neck-cancer-cells-to-artesunate-induced-ferroptosis
#16
Jong-Lyel Roh, Eun Hye Kim, Hyejin Jang, Daiha Shin
: Artesunate, an anti-malarial drug, has been repurposed as an anticancer drug due to its induction of cell death via reactive oxygen species (ROS) production. However, the molecular mechanisms regulating cancer cell death and the resistance of cells to artesunate remain unclear. We investigated the molecular mechanisms behind the antitumor effects of artesunate and an approach to overcome artesunate resistance in head and neck cancer (HNC). The effects of artesunate and trigonelline were tested in different HNC cell lines, including three cisplatin-resistant HNC cell lines...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28012209/link-between-er-stress-ppar-alpha-activation-and-bet-inhibition-in-relation-to-apolipoprotein-a-i-transcription-in-hepg2-cells
#17
Sophie E van der Krieken, Herman E Popeijus, Ronald P Mensink, Jogchum Plat
Activating transcription factor peroxisome proliferator-activated receptor alpha (PPARα) may increase apoA-I transcription. Furthermore, Bromodomain and Extra-Terminal domain (BET) protein inhibitors increase, whereas Endoplasmic Reticulum (ER) stress decreases apoA-I transcription. We examined possible links between these processes as related to apoA-I transcription in HepG2 cells. JQ1(+), thapsigargin and GW7647 were used to induce respectively BET inhibition, ER-stress and PPARα activation. Expression of ER-stress markers (CHOP, XBP1s) was analyzed by western blotting...
December 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28002939/chicoric-acid-ameliorates-lipopolysaccharide-induced-oxidative-stress-via-promoting-the-keap1-nrf2-transcriptional-signaling-pathway-in-bv-2-microglial-cells-and-mouse-brain
#18
Qian Liu, Yaya Hu, Youfang Cao, Ge Song, Zhigang Liu, Xuebo Liu
As a major nutraceutical component of a typical Mediterranean vegetable chicory, chicoric acid (CA) has been well-documented due to its excellent antioxidant and antiobesity bioactivities. In the current study, the effects of CA on lipopolysaccharide (LPS)-stimulated oxidative stress in BV-2 microglia and C57BL/6J mice and the underlying molecular mechanisms were investigated. Results demonstrated that CA significantly reversed LPS-elicited cell viability decrease, mitochondrial dysfunction, activation of NFκB and MAPK stress pathways, and inflammation responses via balancing cellular redox status...
January 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27999449/the-ratio-of-hmox1-nrf2-mrna-level-in-the-tumor-tissue-is-a-predictor-of-distant-metastasis-in-colorectal-cancer
#19
Liang-Che Chang, Chung-Wei Fan, Wen-Ko Tseng, Hui-Ping Chein, Tsan-Yu Hsieh, Jim-Ray Chen, Cheng-Cheng Hwang, Chung-Ching Hua
Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction...
2016: Disease Markers
https://www.readbyqxmd.com/read/27998394/the-hypertension-drug-verapamil-activates-nrf2-by-promoting-p62-dependent-autophagic-keap1-degradation-and-prevents-acetaminophen-induced-cytotoxicity
#20
Da Hyun Lee, Jeong Su Park, Yu Seol Lee, Su Haeng Sung, Yong-Ho Lee, Soo Han Bae
Nuclear factor erythroid 2-related factor 2 (Nrf2) provides cellular defense against oxidative stress by inducing the expression of antioxidant and detoxification enzymes. The calcium antagonist verapamil is an FDA-approved drug prescribed for the treatment of hypertension. Here, we show that verapamil acts as a potent Nrf2 activator without causing cytotoxicity through degradation of Kelch-like ECH-associated protein 1 (Keap1), an Nrf2 repressor. Furthermore, verapamil-induced Keap1 degradation is prominently mediated by a p62-dependent autophagic pathway...
December 20, 2016: BMB Reports
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