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https://www.readbyqxmd.com/read/28645578/the-electrophilic-character-of-quinones-is-essential-for-the-suppression-of-bach1
#1
Chuanyang Su, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important cellular defense mechanisms against oxidative attack. BTB and CNC homology-1 (Bach1), like Kelch-like ECH-associated protein 1 (Keap1), is one of a negative regulator of Nrf2 that control antioxidant response elements (ARE)-dependent gene expressions. In the current study, we found that quinones show greater capacity than hydroquinones in nuclear Bach1 export, as well as ubiquitin-dependent Bach1 degradation in our experimental time frame...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28598815/prediction-of-clinical-outcome-and-survival-in-soft-tissue-sarcoma-using-a-ten-lncrna-signature
#2
Rong-Quan He, Qing-Jun Wei, Rui-Xue Tang, Wen-Jie Chen, Xia Yang, Zhi-Gang Peng, Xiao-Hua Hu, Jie Ma, Gang Chen
The prognostic value of long non-coding RNAs (lncRNAs) in patients with soft-tissue sarcoma has rarely been unraveled. The aim of the study was to find a lncRNA signature to predict the clinical outcome and survival in soft-tissue sarcoma based on the high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA) database. The lncRNAs which closely correlated with overall survival in 258 soft-tissue sarcoma patients were identified with Cox proportional regression model. Ten lncRNAs, including RP11-560J1...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588024/bet-inhibitors-block-the-epstein-barr-virus-lytic-cycle-at-two-distinct-steps
#3
Kristin M Keck, Stephanie A Moquin, Amanda He, Samantha G Fernandez, Jessica J Somberg, Stephanie M Liu, Delsy M Martinez, Jj L Miranda
Lytic infection by the Epstein-Barr virus (EBV) poses numerous health risks, such as infectious mononucleosis and lymphoproliferative disorder. Proteins in the bromodomain and extraterminal (BET) family regulate multiple stages of viral life cycles and provide promising intervention targets. Synthetic small molecules can bind to the bromodomains and disrupt function by preventing recognition of acetylated lysine substrates. We demonstrate that JQ1 and other BET inhibitors block two different steps in the sequential cascade of the EBV lytic cycle...
June 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28576353/reprint-of-heme-oxygenase-1-affects-granulopoiesis-in-mice-through-control-of-myelocyte-proliferation
#4
Karolina Bukowska-Strakova, Maciej Ciesla, Krzysztof Szade, Witold Norbert Nowak, Robert Straka, Agata Szade, Malgorzata Tyszka-Czochara, Karolina Najder, Anna Konturek, Maciej Siedlar, Jozef Dulak, Alicja Jozkowicz
Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe(2+). We showed that HO-1 knock-out mice (HO-1(-/-)) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced surface expression of G-CSF receptor on the hematopoietic precursors. This suggests the effect of HO-1 on granulopoiesis. Here we aimed to determine the stage of granulopoiesis regulated by HO-1...
June 2017: Immunobiology
https://www.readbyqxmd.com/read/28536120/hepatocyte-specific-sirtuin-6-deletion-predisposes-to-nonalcoholic-steatohepatitis-by-up-regulation-of-bach1-an-nrf2-repressor
#5
Sun-O Ka, In Hyuk Bang, Eun Ju Bae, Byung-Hyun Park
Sirtuin (Sirt)6 has been implicated in negative regulation of inflammation and lipid metabolism, although its function in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains to be defined. To explore the role of hepatocyte Sirt6 in NASH development, we generated hepatocyte-specific Sirt6 knockout (KO) mice that were fed a high-fat and high-fructose (HFHF) diet for 16 wk. HFHF-fed KO mice had increased hepatic steatosis and inflammation and aggravated glucose intolerance and insulin resistance compared with wild-type mice...
May 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28420366/pirfenidone-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice-by-regulating-nrf2-bach1-equilibrium
#6
Yuan Liu, Fuai Lu, Lirong Kang, Zhihua Wang, Yongfu Wang
BACKGROUND: Oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the expression level of antioxidant factors, further regulating the function of oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for IPF therapy approved drugs...
April 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28392885/the-transcription-factor-bach1-suppresses-the-developmental-angiogenesis-of-zebrafish
#7
Li Jiang, Meng Yin, Jie Xu, Mengping Jia, Shaoyang Sun, Xu Wang, Jianyi Zhang, Dan Meng
Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28349828/silencing-of-bach1-gene-by-small-interfering-rna-mediation-regulates-invasive-and-expression-level-of-mir-203-mir-145-matrix-metalloproteinase-9-and-cxcr4-receptor-in-mda-mb-468-breast-cancer-cells
#8
Reza Mohammadzadeh, Mojgan Saeid Harouyan, Seyed Mansour Ale Taha
BACKGROUND: Recently experimental validation of the networks revealed bach1, a basic leucine zipper transcription factor, as the common regulator of several functional invasive genes. The expression of bach1 and its target genes was linked to the higher risk of breast cancer recurrence in patients. The aim of this study was to investigate the effect of specific bach1 small interfering RNAs, on the invasive and expression level of miR-203, miR-145, matrix metalloproteinase-9, and CXCR4 receptor which play a role in cancer metastasis, in MDA-MB-468 cell lines...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28347842/potential-role-of-heme-metabolism-in-the-inducible-expression-of-heme-oxygenase-1
#9
Aka-Aki Takeda, Machiko Sasai, Yuka Adachi, Keiko Ohnishi, Jun-Ichi Fujisawa, Shingo Izawa, Shigeru Taketani
BACKGROUND: The degradation of heme significantly contributes to cytoprotective effects against oxidative stress and inflammation. The enzyme heme oxygenase-1 (HO-1), involved in the degradation of heme, forms carbon monoxide (CO), ferrous iron, and bilirubin in conjunction with biliverdin reductase, and is induced by various stimuli including oxidative stress and heavy metals. We examined the involvement of heme metabolism in the induction of HO-1 by the inducers sulforaphane and sodium arsenite...
March 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28245982/comparative-analysis-of-microrna-and-mrna-expression-profiles-in-cells-and-exosomes-under-toluene-exposure
#10
Jung-Hee Lim, Mi-Kyung Song, Yoon Cho, Woong Kim, Sung Ok Han, Jae-Chun Ryu
Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28213091/convergence-of-hepcidin-deficiency-systemic-iron-overloading-heme-accumulation-and-rev-erb%C3%AE-%C3%AE-activation-in-aryl-hydrocarbon-receptor-elicited-hepatotoxicity
#11
Kelly A Fader, Rance Nault, Mathew P Kirby, Gena Markous, Jason Matthews, Timothy R Zacharewski
Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01-30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses...
April 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28142143/nrf2-and-bach1-may-play-a-role-in-the-modulation-of-ultraviolet-a-induced-oxidative-stress-by-acetyl-11-keto-%C3%AE-boswellic-acid-in-skin-keratinocytes
#12
Shiying Yang, Bin Zhou, Wei Xu, Fangfang Xue, Muhammad Farrukh Nisar, Chunxiang Bian, Xiao Huang, Li Yang, Yiguo Zhang, Jörg W Bartsch, Julia Li Zhong
BACKGROUND: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. OBJECTIVE: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. METHODS: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined...
2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28123399/the-status-of-nrf2-based-therapeutics-current-perspectives-and-future-prospects
#13
REVIEW
Irina G Gazaryan, Bobby Thomas
This mini-review presents the authors' vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. There are two opposite "chemical" mechanisms underlying such activation: the first one is a non-specific covalent modification of Keap1 thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28120861/intracellular-degradation-of-functionalized-carbon-nanotube-iron-oxide-hybrids-is-modulated-by-iron-via-nrf2-pathway
#14
Dan Elgrabli, Walid Dachraoui, Hélène de Marmier, Cécilia Ménard-Moyon, Dominique Bégin, Sylvie Bégin-Colin, Alberto Bianco, Damien Alloyeau, Florence Gazeau
The in vivo fate and biodegradability of carbon nanotubes is still a matter of debate despite tremendous applications. In this paper we describe a molecular pathway by which macrophages degrade functionalized multi-walled carbon nanotubes (CNTs) designed for biomedical applications and containing, or not, iron oxide nanoparticles in their inner cavity. Electron microscopy and Raman spectroscopy show that intracellularly-induced structural damages appear more rapidly for iron-free CNTs in comparison to iron-loaded ones, suggesting a role of iron in the degradation mechanism...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108387/inhibition-of-monoamine-oxidase-b-by-selegiline-reduces-cigarette-smoke-induced-oxidative-stress-and-inflammation-in-airway-epithelial-cells
#15
Yuting Cui, Kenneth W K Liu, Yingmin Liang, Mary S M Ip, Judith C W Mak
Chronic obstructive pulmonary disease (COPD) is caused by the build-up of oxidative stress-induced damages due to cigarette smoking, but how monoamine oxidase (MAO)-B signaling is involved remains unclear. This study aims to establish the involvement of MAO-B signaling pathways in cigarette smoke medium (CSM)-induced oxidative stress and inflammation in human airway epithelial cells (AECs). CSM treatment increased MAO-B activity, ROS levels and IL-8 release in AECs. Pretreatment with MAO-B selective inhibitor selegiline reversed the CSM-induced changes in MAO-B activity, ROS levels and IL-8 release in a dose-dependent manner...
February 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28099425/genetic-ablation-of-bach1-gene-enhances-recovery-from-hyperoxic-lung-injury-in-newborn-mice-via-transient-upregulation-of-inflammatory-genes
#16
Masato Ito, Nobuhiko Nagano, Yukio Arai, Ryo Ogawa, Shingo Kobayashi, Yukiko Motojima, Hayato Go, Masanori Tamura, Kazuhiko Igarashi, Phyllis A Dennery, Fumihiko Namba
BACKGROUND: BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase (HO)-1. The effects of Bach1 disruption on hyperoxic lung injury in newborn mice have not been determined. We aimed to investigate the role of Bach1 in the newborns exposed to hyperoxia. METHODS: Bach1(-/-) and WT newborn mice were exposed to 21% or 95% oxygen for 4 d and were then allowed to recover in room air. Lung histology was assessed and lung Bach1, HO-1, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 mRNA levels were evaluated using RT-PCR...
June 2017: Pediatric Research
https://www.readbyqxmd.com/read/28092843/therapeutic-effects-of-bach1-sirna-on-human-breast-adenocarcinoma-cell-line
#17
Mansoor Aletaha, Behzad Mansoori, Ali Mohammadi, Mehdi Fazeli, Behzad Baradaran
BACKGROUND: Despite the great improvements in clinical and therapeutic techniques in recent years, many advanced breast cancer patients still died of the postoperative recurrence and metastasis of disease. Bach1 plays a role in the development of the invasive phenotypes of cancer, cell division and apoptosis in tumor cells. The aim of this study was to investigate the effect of specific bach1 siRNAs, on the proliferation, migration, invasive, induction of apoptosis, cell cycle arrest and alter EMT related miRNA of MDA-MB-468 cells (breast cancer)...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#18
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...
March 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28064106/neuroprotective-effects-of-erythropoietin-against-sevoflurane-induced-neuronal-apoptosis-in-primary-rat-cortical-neurons-involving-the-epor-erk1-2-nrf2-bach1-signal-pathway
#19
Dong-Xue Zhang, Li-Min Zhang, Xiao-Chun Zhao, Wenbo Sun
OBJECTIVE: Erythropoietin (EPO)-induced activation of the EPO receptor (EPOR) against sevoflurane-induced neuronal apoptosis is an effective intervention, but the underlying mechanism is poorly understood. Previous studies have shown that alteration of the nuclear factor erythroid 2-related factor (Nrf2)/BTB-to-CNC homology 1 (Bach1) ratio by extracellular signal-related kinases (Erk) 1/2 ameliorates the oxidative stress which occurs in human macrophages. In this study, we determined whether or not EPO attenuates sevoflurane-induced neuronal apoptosis via the EPOR-Erk1/2-Nrf2/Bach1 signal pathway...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28000777/bach1-promotes-temozolomide-resistance-in-glioblastoma-through-antagonizing-the-function-of-p53
#20
Er Nie, Xin Jin, Weining Wu, Tianfu Yu, Xu Zhou, Tongle Zhi, Zhumei Shi, Junxia Zhang, Ning Liu, Yongping You
The acquisition of drug resistance is a persistent clinical problem limiting the successful treatment of glioblastoma (GBM). However, the molecular mechanisms by which initially chemoresponsive tumors develop therapeutic resistance remain poorly understood. In this study, we report that BACH1, a heme-binding protein that participates in transcriptional repression or activation, was significantly upregulated in glioblastoma tissues. Overexpression of BACH1 in GBM cells conferred resistance to temozolomide, whereas its inhibition markedly sensitized resistant cells to temozolomide in vitro and in vivo...
December 21, 2016: Scientific Reports
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