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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
#1
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...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28194437/mitochondrial-quality-control-dysregulation-in-conditional-ho-1-mice
#2
Hagir B Suliman, Jeffrey E Keenan, Claude A Piantadosi
The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM](-/-)) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)(-/-) hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28179208/association-between-a-heme-oxygenase-2-genetic-variant-and-risk-of-parkinson-s-disease-in-han-chinese
#3
Sijia Tian, Xinglong Yang, Quanzhen Zhao, Jinhua Zheng, Hongyan Huang, Yalan Chen, Ran An, Yanming Xu
Studies have reported conflicting results about possible associations between variants in heme oxygenase (HMOX) genes and risk of Parkinson's disease (PD) in Caucasians, and little is known about these associations in Asians. We genotyped the single-nucleotide polymorphisms (SNPs) rs2071746 and rs2071747 in HMOX1 and rs1051308 in HMOX2 in 583 Han Chinese with PD and 627 healthy controls using a customized 2×48-Plex SNP Scan™ kit. Frequencies of genotypes and minor alleles were similar between patients and controls for rs2071746 and rs2071747, but different for rs1051308(P=0...
February 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28177777/high-concentration-calcitriol-induces-endoplasmic-reticulum-stress-related-gene-profile-in-breast-cancer-cells
#4
Ali Burak Ozkaya, Handan Ak, Hikmet Hakan Aydin
Calcitriol, the active form of vitamin D, is known for its anti-cancer properties including induction of apoptosis, inhibition of angiogenesis and metastasis. Understanding the mechanism of action for calcitriol will help development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters ER stress markers, therefore in this study we have focused on ER-stress related genes to reveal calcitriols action on these genes in particular...
June 29, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28167288/impact-of-tet2-deficiency-on-iron-metabolism-in-erythroblasts
#5
Kyoko Inokura, Tohru Fujiwara, Kei Saito, Tatsuya Iino, Shunsuke Hatta, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Kenichi Ishizawa, Kazuya Shimoda, Hideo Harigae
Sideroblastic anemia is characterized by the presence of ring sideroblasts, which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both acquired and congenital forms of sideroblastic anemia. However, the mechanism leading to ring sideroblast formation remains elusive. Acquired sideroblastic anemia is usually observed in myelodysplastic syndrome. Because a subset of myelodysplastic syndrome harbors a somatic mutation of TET2, it may be involved in iron metabolism and/or heme biosynthesis in erythroblasts...
February 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28129777/diesel-exhaust-alters-the-response-of-cultured-primary-bronchial-epithelial-cells-from-patients-with-chronic-obstructive-pulmonary-disease-copd-to-non-typeable-haemophilus-influenzae
#6
Maria C Zarcone, Annemarie van Schadewijk, Evert Duistermaat, Pieter S Hiemstra, Ingeborg M Kooter
BACKGROUND: Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied...
January 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28115643/zno-nanoparticles-induced-reactive-oxygen-species-promotes-multimodal-cyto-and-epigenetic-toxicity
#7
Samrat Roy Choudhury, Josue Ordaz, Chiao-Ling Lo, Nur P Damayanti, Feng Zhou, Joseph Irudayaraj
In this study we evaluated and correlated the cytotoxic effects of zinc oxide nanoparticles (ZnO-NPs) to epigenetic modifications, using human embryonic kidney (HEK-293) cells as a model system. Imaging of singlet and total reactive oxygen species (ROS) in ZnO-NPs treated live cells was performed followed by the evaluation of its effects on cytoskeletal, mitochondrial, and nuclear integrity, and on the expression of ROS responsive genes. Next, we determined the global and locus specific changes in DNA-methylation at the three genomic repeat sequences namely global LINE-1, subtelomeric D4Z4 and pericentromeric NBL2, and at the promoter of selected ROS responsive genes (AOX1, HMOX1, NCF2, SOD3)...
January 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28102348/ho-1-inhibits-preadipocyte-proliferation-and-differentiation-at-the-onset-of-obesity-via-ros-dependent-activation-of-akt2
#8
Gabriel Wagner, Josefine Lindroos-Christensen, Elisa Einwallner, Julia Husa, Thea-Christin Zapf, Katharina Lipp, Sabine Rauscher, Marion Gröger, Andreas Spittler, Robert Loewe, Florian Gruber, J Catharina Duvigneau, Thomas Mohr, Hedwig Sutterlüty-Fall, Florian Klinglmüller, Gerhard Prager, Berthold Huppertz, Jeanho Yun, Oswald Wagner, Harald Esterbauer, Martin Bilban
Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors, however, the underlying molecular mechanisms remain unclear. Here, we used an unbiased transcriptomics approach to identify the earliest molecular underpinnings occuring in adipose precursors following a brief HFD in mice. Our analysis identifies Heme Oxygenase-1 (HO-1) as strongly and selectively being upregulated in the adipose precursor fraction of WAT, upon high-fat diet (HFD) feeding...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100868/growth-inhibition-of-refractory-human-gallbladder-cancer-cells-by-retinol-and-its-mechanism-of-action
#9
Chuan Li, Masahiko Imai, Shinya Hasegawa, Masahiro Yamasaki, Noriko Takahashi
Among the constituents of the essential nutrient vitamin A, retinol is a potent suppressor of refractory cancer cell growth linked to tumor progression, showing greater efficacy than retinoic acid (RA). However, the mechanisms of retinol action on human refractory cancer are not known well. In the current study, we examined the actions of retinol on proliferation of human gallbladder cancer NOZ C-1 cells. Retinol and RA inhibited the proliferation of human NOZ C-1 cells in dose-dependent manner, while RA was less potent than retinol...
January 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#10
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28074863/herb-pair-danggui-honghua-mechanisms-underlying-blood-stasis-syndrome-by-system-pharmacology-approach
#11
Shi-Jun Yue, Lan-Ting Xin, Ya-Chu Fan, Shu-Jiao Li, Yu-Ping Tang, Jin-Ao Duan, Hua-Shi Guan, Chang-Yun Wang
Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28055957/analysis-of-molecular-mechanisms-of-5-fluorouracil-induced-steatosis-and-inflammation-in-vitro-and-in-mice
#12
Judith Sommer, Abdo Mahli, Kim Freese, Tobias S Schiergens, Fulya Suzan Kuecuekoktay, Andreas Teufel, Wolfgang E Thasler, Martina Müller, Anja K Bosserhoff, Claus Hellerbrand
Chemotherapy-associated steatohepatitis is attracting increasing attention because it heralds an increased risk of morbidity and mortality in patients undergoing surgery because of liver metastases. The aim of this study was to develop in vitro and in vivo models to analyze the pathogenesis of 5-fluorouracil (5-FU)-induced steatohepatitis.Therefore, primary human hepatocytes and HepG2 hepatoma cells were incubated with 5-FU at non-toxic concentrations up to 24 h. Furthermore, hepatic tissue of C57BL/6N mice was analyzed 24 h after application of a single 5-FU dose (200 mg/kg body weight)...
December 30, 2016: Oncotarget
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
#13
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/27998018/genetic-polymorphism-of-heme-oxygenase-1-promoter-in-the-occurrence-and-severity-of-chronic-obstructive-pulmonary-disease-a-meta-analysis
#14
Hongbin Zhou, Xiwang Ying, Yuanshun Liu, Sa Ye, Jianping Yan, Yaqing Li
Heme oxygenase 1 (HMOX1) plays an important role in the development of chronic obstructive pulmonary disease (COPD). However, the association of HMOX1 length polymorphism in promoter region to the risk and severity of COPD has not been well studied. In this study, we searched the databases including PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) and extracted the information from related articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study the effect of HMOX1 polymorphism on the risk and severity of COPD...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27979226/fractionation-enzyme-inhibitory-and-cellular-antioxidant-activity-of-bioactives-from-purple-sweet-potato-ipomoea-batatas
#15
Tuba Esatbeyoglu, Miriam Rodríguez-Werner, Anke Schlösser, Peter Winterhalter, Gerald Rimbach
Sweet potato (Ipomoea batatas L.) is mainly cultivated in Asia. The deep purple color of purple sweet potato (PSP) is due to the high content of acylated anthocyanins. In the present study, PSP-derived polyphenols were identified using HPLC-PDA and HPLC-ESI-MS(n) analyses. After concentration of the polyphenols from PSP, preparative separation into two fractions, designated anthocyanins (AF) and copigments (CF), was carried out using adsorptive membrane chromatography. In enzyme inhibitory assays, all PSP samples inhibited the enzymes α-amylase, α-glucosidase and xanthine oxidase...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27976481/irradiation-with-uv-c-inhibits-tnf-%C3%AE-dependent-activation-of-the-nf-%C3%AE%C2%BAb-pathway-in-a-mechanism-potentially-mediated-by-reactive-oxygen-species
#16
Katarzyna Szoltysek, Anna Walaszczyk, Patryk Janus, Marek Kimmel, Piotr Widlak
Pathways depending on the NF-κB transcription factor are essential components of cellular response to stress. Plethora of stimuli modulating NF-κB includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affecting NF-κB remains relatively understudied. Here, we aim to characterize the influence of UV radiation on TNF-α-induced activity of the NF-κB pathway. We document inhibition of TNF-α-induced activation of NF-κB and subsequent suppression of NF-κB-regulated genes in cells exposed to UV-C several hours before TNF-α stimulation...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27943244/genetic-variations-in-bilirubin-metabolism-genes-and-their-association-with-unconjugated-hyperbilirubinemia-in-adults
#17
Ashish S Chiddarwar, Selma Z D'Silva, Roshan B Colah, Kanjaksha Ghosh, Malay B Mukherjee
OBJECTIVE: The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes (UGT1A1, OATP2, HMOX1, and BLVRA) and their association with hyperbilirubinemia. MATERIAL AND METHODS: Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, GeneScan analysis, and direct DNA sequencing. RESULTS: Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls...
December 12, 2016: Annals of Human Genetics
https://www.readbyqxmd.com/read/27927768/iron-heme-bach1-axis-is-involved-in-erythroblast-adaptation-to-iron-deficiency
#18
Masahiro Kobayashi, Hiroki Kato, Hiroshi Hada, Ari Itoh-Nakadai, Tohru Fujiwara, Akihiko Muto, Yukihiro Inoguchi, Kenji Ichiyanagi, Wataru Houjou, Naohisa Tomosugi, Hiroyuki Sasaki, Hideo Harigae, Kazuhiko Igarashi
Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27829220/gene-expression-profile-induced-by-arsenic-trioxide-in-chronic-lymphocytic-leukemia-cells-reveals-a-central-role-for-heme-oxygenase-1-in-apoptosis-and-regulation-of-matrix-metalloproteinase-9
#19
Irene Amigo-Jiménez, Elvira Bailón, Noemí Aguilera-Montilla, José A García-Marco, Angeles García-Pardo
CLL remains an incurable disease in spite of the many new compounds being tested. Arsenic trioxide (ATO) induces apoptosis in all CLL cell types and could constitute an efficient therapy. To further explore this, we have studied the gene expression profile induced by ATO in CLL cells. ATO modulated many genes, largely involved in oxidative stress, being HMOX1 the most upregulated gene, also induced at the protein level. ATO also increased MMP-9, as we previously observed, both at the mRNA and protein level...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829164/molecular-effects-of-1-naphthyl-methylcarbamate-and-solar-radiation-exposures-on-human-melanocytes
#20
Bianca Ferrucio, Manoela Tiago, Richard D Fannin, Liwen Liu, Kevin Gerrish, Silvya Stuchi Maria-Engler, Richard S Paules, Silvia Berlanga de Moraes Barros
Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100μM) and solar radiation (375mJ/cm(2))...
February 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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