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Iron chelation

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https://www.readbyqxmd.com/read/28432145/bacterial-siderophores-hijack-neutrophil-functions
#1
Piu Saha, Beng San Yeoh, Rodrigo A Olvera, Xia Xiao, Vishal Singh, Deepika Awasthi, Bhagawat C Subramanian, Qiuyan Chen, Madhu Dikshit, Yanming Wang, Carole A Parent, Matam Vijay-Kumar
Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils. We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28429296/diurnal-changes-in-transcript-and-metabolite-levels-during-the-iron-deficiency-response-of-rice
#2
Jamie Selby-Pham, Adrian Lutz, Laura T Moreno-Moyano, Berin A Boughton, Ute Roessner, Alexander A T Johnson
BACKGROUND: Rice (Oryza sativa L.) is highly susceptible to iron (Fe) deficiency due to low secretion levels of the mugineic acid (MA) family phytosiderophore (PS) 2'-deoxymugineic acid (DMA) into the rhizosphere. The low levels of DMA secreted by rice have proved challenging to measure and, therefore, the pattern of DMA secretion under Fe deficiency has been less extensively studied relative to other graminaceous monocot species that secrete high levels of PS, such as barley (Hordeum vulgare L...
December 2017: Rice
https://www.readbyqxmd.com/read/28427888/dopamine-elevates-intracellular-zinc-concentration-in-cultured-rat-embryonic-cortical-neurons-through-the-camp-nitric-oxide-signaling-cascade
#3
Hui-Hsing Hung, Lung-Sen Kao, Pei-Shan Liu, Chien-Chang Huang, De-Ming Yang, Chien-Yuan Pan
Zinc ion (Zn(2+)), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn(2+) concentrations ([Zn(2+)]i) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn(2+)]i and the effect of [Zn(2+)]i in modulating the autophagy in cultured rat embryonic cortical neurons...
April 17, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28426241/extracellular-heme-uptake-and-the-challenge-of-bacterial-cell-membranes
#4
Weiliang Huang, Angela Wilks
Iron is essential for the survival of most bacteria but presents a significant challenge given its limited bioavailability. Furthermore, the toxicity of iron combined with the need to maintain physiological iron levels within a narrow concentration range requires sophisticated systems to sense, regulate, and transport iron. Most bacteria have evolved mechanisms to chelate and transport ferric iron (Fe(3+)) via siderophore receptor systems, and pathogenic bacteria have further lowered this barrier by employing mechanisms to utilize the host's hemoproteins...
April 19, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28421447/inhibition-of-p-glycoprotein-stimulates-cell-death-under-hypoxia-mimicking-conditions
#5
A S Vdovin, P V Maximchik, A V Kulikov, B D Zhivotovsky, V G Gogvadze
The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28421266/reactive-oxygen-species-mediated-t-lymphocyte-abnormalities-in-an-iron-overloaded-mouse-model-and-iron-overloaded-patients-with-myelodysplastic-syndromes
#6
Jie Chen, Wen-Yi Lu, Ming-Feng Zhao, Xiao-Li Cao, Yan-Yu Jiang, Xin Jin, Ping Xu, Ting-Ting Yuan, Yu-Chen Zhang, Xiao Chai, Juan-Xia Meng, Qing Li, Xia Xiao, Juan Mu, De-Guan Li, Ai-Ping Qi
The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3(+) T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes...
April 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28419408/iron-chelating-therapy-with-deferasirox-in-transfusion-dependent-higher-risk-myelodysplastic-syndromes-a-retrospective-multicentre-study
#7
Pellegrino Musto, Luca Maurillo, Vittorio Simeon, Antonella Poloni, Carlo Finelli, Enrico Balleari, Alessandra Ricco, Flavia Rivellini, Agostino Cortelezzi, Giuseppe Tarantini, Oreste Villani, Giovanna Mansueto, Maria R Milella, Daniele Scapicchio, Gioacchino Marziano, Massimo Breccia, Pasquale Niscola, Alessandro Sanna, Cristina Clissa, Maria T Voso, Susanna Fenu, Adriano Venditti, Valeria Santini, Emanuele Angelucci, Alessandro Levis
Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75)...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28415737/peroxynitrite-dominates-sodium-nitroprusside-induced-apoptosis-in-human-hepatocellular-carcinoma-cells
#8
Ying-Yao Quan, Yu-Hong Liu, Chun-Mei Lin, Xiao-Ping Wang, Tong-Sheng Chen
This study aims to explore which radicals dominate sodium nitroprusside (SNP)-induced cytotoxicity in human hepatocellular carcinoma (HCC) cells (HepG2 and Hep3B). Exposure of SNP to cell medium produced abundant nitric oxide (NO), superoxide anion (O2•-), hydrogen peroxide (H2O2) and iron ions. SNP potently induced caspases activation, mitochondrial membrane permeabilization and apoptosis in HCC cells. In Hep3B cells, pretreatment with NO scavenger (PTIO) did not prevent SNP-induced cytotoxicity. However, in HepG2 cells, SNP-induced cytotoxicity was prevented significantly by pretreatment with PTIO and O2•- scavenger, and especially was almost completely blocked by pretreatment with FeTPPS (peroxynitrite scavenger)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405169/oxidant-induced-autophagy-and-ferritin-degradation-contribute-to-epithelial-mesenchymal-transition-through-lysosomal-iron
#9
Apostolos Sioutas, Linda K Vainikka, Magnus Kentson, Sören Dam-Larsen, Urban Wennerström, Petra Jacobson, Hans Lennart Persson
PURPOSE: Transforming growth factor (TGF)-β1 triggers epithelial-mesenchymal transition (EMT) through autophagy, which is partly driven by reactive oxygen species (ROS). The aim of this study was to determine whether leaking lysosomes and enhanced degradation of H-ferritin could be involved in EMT and whether it could be possible to prevent EMT by iron chelation targeting of the lysosome. MATERIALS AND METHODS: EMT, H-ferritin, and autophagy were evaluated in TGF-β1-stimulated A549 human lung epithelial cells cultured in vitro using Western blotting, with the additional morphological assessment of EMT...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28404780/environmental-modification-via-a-quorum-sensing-molecule-influences-the-social-landscape-of-siderophore-production
#10
Roman Popat, Freya Harrison, Ana C da Silva, Scott A S Easton, Luke McNally, Paul Williams, Stephen P Diggle
Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed 'public goods' because they are costly for individuals to produce and can be exploited by non-producers (cheats). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS, therefore, determines the cooperative phenotype of individuals, and influences conflict over public goods...
April 12, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28404645/irp2-as-a-potential-modulator-of-cell-proliferation-apoptosis-and-prognosis-in-nonsmall-cell-lung-cancer
#11
Heena Khiroya, Jasbir S Moore, Nabeel Ahmad, Jamie Kay, Kerry Woolnough, Gerald Langman, Iyad Ismail, Babu Naidu, Chris Tselepis, Alice M Turner
IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which is critical to intracellular iron homeostasis and which relates to the rate of cellular proliferation. IREB2 lies in a lung cancer susceptibility locus. The aims were to assess 1) the relationship between iron loading, cell proliferation and IRP2 expression in lung cancer; 2) the potential of iron related pathways as therapeutic targets; and 3) the relevance of IRP2 in operated lung cancer patients.Cells of two nonsmall cell cancer (NSCLC) lines and primary bronchial epithelial cells (PBECs) were cultured with and without iron; and proliferation, apoptosis and migration were assessed...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28404539/a-national-registry-of-thalassemia-in-turkey-demographic-and-disease-characteristics-of-patients-achievements-and-challenges-in-prevention
#12
Yeşim Aydınok, Yeşim Oymak, Berna Atabay, Gönül Aydoğan, Akif Yeşilipek, Selma Ünal, Yurdanur Kılınç, Banu Oflaz, Mehmet Akın, Canan Vergin, Melike Sezgin Evim, Ümran Çalışkan, Şule Ünal, Ali Bay, Elif Kazancı, Dilber Talia İleri, Didem Atay, Türkan Patıroğlu, Selda Kahraman, Murat Söker, Mediha Akcan, Aydan Akdeniz, Mustafa Büyükavcı, Güçhan Alanoğlu, Özcan Bör, Nur Soyer, Nihal Özdemir Karadaş, Ezgi Uysalol, Meral Türker, Arzu Akçay, Süheyla Ocak, Adalet Meral Güneş, Hüseyin Tokgöz, Zümrüt Uysal, Naci Tiftik, Zeynep Karakaş
Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate demographic and disease characteristics of patients, and assessed the efficacy of hemoglobinopathy control program (HCP) over 10 years in Turkey. A total of 2046 patients from 27 Thalassemia Centers were registered in which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). The majority of patients were accumulated into the costal areas of Turkey...
April 13, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28401463/crop-specific-plant-growth-promoting-effects-of-accd-enzyme-and-siderophore-producing-and-cynogenic-fluorescent-pseudomonas
#13
Priyanka, Toshy Agrawal, Anil S Kotasthane, Ashok Kosharia, Renu Kushwah, Najam Waris Zaidi, U S Singh
Fluorescent Pseudomonas, aerobic, Gram-negative bacteria possess many traits that make them well suited as biocontrol and growth promoting agents. Our study revealed that isolates vary in mechanisms involved in the antagonist interactions against pathogen and growth stimulatory effects on host plant. Most of the potential antagonistic fluorescent Pseudomonas identified were avid iron chelators (P233, P201, 176, P76 and, P76). Wide variation in ACCd enzyme production was observed. ACCd enzyme assay tested P141 > P247 > P126, as potential ACCd enzyme producer...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28399703/value-of-speckle-tracking-echocardiography-for-detection-of-clinically-silent-left-ventricular-dysfunction-in-patients-with-%C3%AE-thalassemia
#14
Mozhgan Parsaee, Sedigheh Saedi, Pegah Joghataei, Azita Azarkeivan, Zahra Alizadeh Sani
OBJECTIVE: β-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring chronic transfusion therapy. Cardiac involvement is the main cause of death in patients with thalassemia major. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) dysfunction in patients with thalassemia. Therefore, we need novel parameters in different imaging techniques to discover cardiac involvement in an early and subtle stage...
April 12, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28399452/design-synthesis-and-evaluation-of-curcumin-derivatives-as-nrf2-activators-and-cytoprotectors-against-oxidative-death
#15
Zhi-Shan Tu, Qi Wang, Dan-Dan Sun, Fang Dai, Bo Zhou
Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells...
April 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28396543/a-topical-hydrogel-with-deferiprone-and-gallium-protoporphyrin-targets-bacterial-iron-metabolism-and-has-antibiofilm-activity
#16
Katharina Richter, Nicky Thomas, Jolien Claeys, Jonathan McGuane, Clive A Prestidge, Tom Coenye, Peter-John Wormald, Sarah Vreugde
Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. Whilst oral drug-delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection-site while reducing systemic side-effects.This study determined the antibiofilm activity of a surgical wound-gel loaded with the iron-chelator deferiprone (Def) and the heme-analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin...
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28396286/altered-mitochondrial-and-peroxisomal-integrity-in-lipocalin-2-deficient-mice-with-hepatic-steatosis
#17
Anastasia Asimakopoulou, Annabelle Fülöp, Erawan Borkham-Kamphorst, Eddy Van de Leur, Nikolaus Gassler, Thorsten Berger, Birte Beine, Helmut E Meyer, Tak W Mak, Carsten Hopf, Corinna Henkel, Ralf Weiskirchen
Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis, we performed a comparative profiling of proteins and lipids of wild type (WT) and Lcn2-deficient mice fed either standard chow or a methionine- and choline-deficient (MCD) diet...
April 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28395774/determination-of-elemental-composition-of-metals-using-ambient-organic-mass-spectrometry
#18
Christopher Shiea, Yeou-Lih Huang, Sy-Chyi Cheng, Yi-Lun Chen, Jentaie Shiea
Conventional inorganic mass spectrometric (MS) analysis of metals can require time-consuming and tedious sample preparation. We thus report the novel and direct characterization of metals in solid samples using an organic MS technique known as electrospray laser desorption ionization mass spectrometry (ELDI/MS). No sample pretreatment was needed, and results were rapidly obtained due to the ambient and laser-based nature of ELDI/MS. Metals from samples were desorbed and ionized by laser irradiation, after which they reacted with EDTA and then post-ionized and detected as metal-EDTA complexes...
May 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28394491/randomized-blinded-placebo-and-positive-controlled-crossover-study-to-determine-the-effect-of-deferiprone-on-the-qtc-interval-in-healthy-subjects
#19
Caroline Fradette, Anna Rozova, Anne Stilman, Yu Chung Tsang, Mark J Allison, Fernando Tricta
This study evaluated whether deferiprone, an oral iron chelator, acts to prolong the QT interval. Fifty healthy volunteers received single doses of each of the following: therapeutic dose of deferiprone (33 mg/kg), supratherapeutic dose (50 mg/kg), placebo, or moxifloxacin, a positive control known to significantly prolong QT interval. Following each dose, subjects underwent cardiac monitoring, pharmacokinetics assessments, and safety assessments. Based on the QT interval obtained using the Fridericia correction for heart rate (QTcF), the upper bound of the 1-sided 95% confidence interval of the mean difference between deferiprone and placebo was <10 milliseconds (the threshold of concern defined by authorities) at all time points for both doses: maximum difference of 3...
April 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28389407/d-penicillamine-combined-with-inhibitors-of-hydroperoxide-metabolism-enhances-lung-and-breast-cancer-cell-responses-to-radiation-and-carboplatin-via-h2o2-mediated-oxidative-stress
#20
Sebastian J Sciegienka, Shane R Solst, Kelly C Falls, Joshua D Schoenfeld, Adrienne R Klinger, Natalie L Ross, Samuel N Rodman, Douglas R Spitz, Melissa A Fath
D-penicillamine (DPEN), a copper chelator, has been used in the treatment of Wilson's disease, cystinuria, and rheumatoid arthritis. Recent evidence suggests that DPEN in combination with biologically relevant copper (Cu) concentrations generates H2O2 in cancer cell cultures, but the effects of this on cancer cell responses to ionizing radiation and chemotherapy are unknown. Increased steady-state levels of H2O2 were detected in MB231 breast and H1299 lung cancer cells following treatment with DPEN (100µM) and copper sulfate (15µM)...
April 5, 2017: Free Radical Biology & Medicine
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