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Ferroportin

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https://www.readbyqxmd.com/read/28203649/increased-iron-export-by-ferroportin-induces-restriction-of-hiv-1-infection-in-sickle-cell-disease
#1
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Adv
https://www.readbyqxmd.com/read/28188131/momelotinib-inhibits-acvr1-alk2-decreases-hepcidin-production-and-ameliorates-anemia-of-chronic-disease-in-rodents
#2
Malte Asshoff, Verena Petzer, Matthew R Warr, David Haschka, Piotr Tymoszuk, Egon Demetz, Markus Seifert, Wilfried Posch, Manfred Nairz, Pat Maciejewski, Peter Fowles, Christopher J Burns, Gregg Smith, Kay-Uwe Wagner, Guenter Weiss, J Andrew Whitney, Igor Theurl
Patients with myelofibrosis (MF) often develop anemia and frequently become dependent on red blood cell transfusions. Results from a phase 2 study for the treatment of MF with the Janus kinase1/2 (JAK1/2) inhibitor momelotinib (MMB) demonstrated that MMB treatment ameliorated anemia, unexpected for a JAK1/2 inhibitor, as erythropoietin-mediated JAK2 signaling is essential for erythropoiesis. Using a rat model of anemia of chronic disease (ACD), we now demonstrate that MMB treatment can normalize hemoglobin and red blood cell numbers...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28159226/the-effect-of-amino-acid-deprivation-on-the-transfer-of-iron-through-caco-2-cell-monolayers
#3
Guenievre Roussel, Valerie Stevens, Sarah Cottin, Harry J McArdle
Iron (Fe) metabolism is modified by many nutritional factors. Amino acids (AA) play a central role in various biological processes, such as protein synthesis and energy supply. However, the influence of AA status on iron metabolism has not been investigated. Here, we test whether AA alters iron metabolism in an intestinal cell model. Both Fe uptake and transfer across the cell monolayer were significantly increased by non-essential AA deficiency (both p<0.001) while only Fe transfer was increased by essential AA deficiency (p<0...
March 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28143953/hemolytic-anemia-repressed-hepcidin-level-without-hepatocyte-iron-overload-lesson-from-g%C3%A3-nther-disease-model
#4
Sarah Millot, Constance Delaby, Boualem Moulouel, Thibaud Lefebvre, Nathalie Pilard, Nicolas Ducrot, Cécile Ged, Philippe Lettéron, Lucia de Franceschi, Jean Charles Deybach, Carole Beaumont, Laurent Gouya, Hubert De Verneuil, Saïd Lyoumi, Hervé Puy, Zoubida Karim
Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1...
February 2017: Haematologica
https://www.readbyqxmd.com/read/28118841/copper-chelation-and-interleukin-6-proinflammatory-cytokine-effects-on-expression-of-different-proteins-involved-in-iron-metabolism-in-hepg2-cell-line
#5
Luca Marco Di Bella, Roberto Alampi, Flavia Biundo, Giovanni Toscano, Maria Rosa Felice
BACKGROUND: In vertebrates, there is an intimate relationship between copper and iron homeostasis. Copper deficiency, which leads to a defect in ceruloplasmin enzymatic activity, has a strong effect on iron homeostasis resulting in cellular iron retention. Much is known about the mechanisms underlying cellular iron retention under "normal" conditions, however, less is known about the effect of copper deficiency during inflammation. RESULTS: We show that copper deficiency and the inflammatory cytokine interleukin-6 have different effects on the expression of proteins involved in iron and copper metabolism such as the soluble and glycosylphosphtidylinositol anchored forms of ceruloplasmin, hepcidin, ferroportin1, transferrin receptor1, divalent metal transporter1 and H-ferritin subunit...
January 24, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/28099381/daily-propranolol-administration-reduces-persistent-injury-associated-anemia-following-severe-trauma-and-chronic-stress
#6
Ines G Alamo, Kolenkode B Kannan, Letitia E Bible, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis...
January 17, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28096133/regulation-of-the-iron-homeostatic-hormone-hepcidin
#7
REVIEW
Veena Sangkhae, Elizabeta Nemeth
Iron is required for many biological processes but is also toxic in excess; thus, body iron balance is maintained through sophisticated regulatory mechanisms. The lack of a regulated iron excretory mechanism means that body iron balance is controlled at the level of absorption from the diet. Iron absorption is regulated by the hepatic peptide hormone hepcidin. Hepcidin also controls iron release from cells that recycle or store iron, thus regulating plasma iron concentrations. Hepcidin exerts its effects through its receptor, the cellular iron exporter ferroportin...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28077896/study-of-scientific-production-of-community-medicines-department-indexed-in-isi-citation-databases
#8
Mohammad Khademloo, Ali Akbar Khaseh, Hasan Siamian, Kobra Aligolbandi, Mahsoomeh Latifi, Mousa Yaminfirooz
BACKGROUND: In the scientometric, the main criterion in determining the scientific position and ranking of the scientific centers, particularly the universities, is the rate of scientific production and innovation, and in all participations in the global scientific development. One of the subjects more involved in repeatedly dealt with science and technology and effective on the improvement of health is medical science fields. In this research using scientometric and citation analysis, we studied the rate of scientific productions in the field of community medicine, which is the numbers of articles published and indexed in ISI database from 2000 to 2010...
October 2016: Acta Informatica Medica: AIM
https://www.readbyqxmd.com/read/28068331/modelling-systemic-iron-regulation-during-dietary-iron-overload-and-acute-inflammation-role-of-hepcidin-independent-mechanisms
#9
Mihaela Enculescu, Christoph Metzendorf, Richard Sparla, Maximilian Hahnel, Johannes Bode, Martina U Muckenthaler, Stefan Legewie
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28054602/identification-of-guanosine-5-diphosphate-as-potential-iron-mobilizer-preventing-the-hepcidin-ferroportin-interaction-and-modulating-the-interleukin-6-stat-3-pathway
#10
Stanzin Angmo, Neha Tripathi, Sheenu Abbat, Shailesh Sharma, Shelley Sardul Singh, Avishek Halder, Kamalendra Yadav, Geeta Shukla, Rajat Sandhir, Vikas Rishi, Prasad V Bharatam, Hariom Yadav, Nitin Kumar Singhal
Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5'-diphosphate (GDP) as a promising hepcidin-binding agent...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28046154/kinetics-of-iron-absorption-by-in-situ-ligated-small-intestinal-loops-of-broilers-involved-in-iron-transporters
#11
L Y Zhang, X D Liao, L Y Zhang, L Lu, X G Luo
Two experiments were conducted with 28-d-old commercial male broilers to study the kinetics of iron (Fe) absorption and the effect of Fe treatment on divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1) mRNA levels in in situ ligated segments from different small intestinal regions of broilers. In Exp. 1, we compared Fe absorption in 3 small intestinal segments at different post-perfusion time points after perfusion with 0.45 m of Fe as Fe sulfate (FeSO ∙ 7HO), and found that the Fe absorption in the duodenum at 30, 45, and 60 min was greater ( < 0...
December 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/28028679/hfe-variants-and-the-expression-of-iron-related-proteins-in-breast-cancer-associated-lymphocytes-and-macrophages
#12
Oriana Marques, Ana Rosa, Luciana Leite, Paula Faustino, Alexandra Rêma, Berta Martins da Silva, Graça Porto, Carlos Lopes
The association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients' HFE genotype...
December 2016: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28027576/human-macrophage-ferroportin-biology-and-the-basis-for-the-ferroportin-disease
#13
Manuela Sabelli, Giuliana Montosi, Cinzia Garuti, Angela Caleffi, Stefania Oliveto, Stefano Biffo, Antonello Pietrangelo
: Ferroportin (FPN1) is the sole iron-exporter in mammals but its cell-specific function and regulation are still elusive. This study aims at studying FPN1 expression in human macrophages, the cells that mostly contribute on a daily basis to plasma iron turnover and are central in the pathogenesis of the disease due to lack-of-function FPN1 mutations, the Ferroportin Disease (FD). We characterized FPN1 protein expression and traffic by confocal microscopy, western blot, gel-filtration and immunoprecipitation studies in macrophages from blood donors and patients with either FPN1 p...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28004654/hepcidin-inhibits-smad3-phosphorylation-in-hepatic-stellate-cells-by-impeding-ferroportin-mediated-regulation-of-akt
#14
Chang Yeob Han, Ja Hyun Koo, Sung Hoon Kim, Sara Gardenghi, Stefano Rivella, Pavel Strnad, Se Jin Hwang, Sang Geon Kim
Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl4 treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGFβ1-mediated Smad3 phosphorylation via Akt...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27999284/aspirin-down-regulates-hepcidin-by-inhibiting-nf-%C3%AE%C2%BAb-and-il6-jak2-stat3-pathways-in-bv-2-microglial-cells-treated-with-lipopolysaccharide
#15
Wan-Ying Li, Fei-Mi Li, Yu-Fu Zhou, Zhong-Min Wen, Juan Ma, Ke Ya, Zhong-Ming Qian
Aspirin down regulates transferrin receptor 1 (TfR1) and up regulates ferroportin 1 (Fpn1) and ferritin expression in BV-2 microglial cells treated without lipopolysaccharides (LPS), as well as down regulates hepcidin and interleukin 6 (IL-6) in cells treated with LPS. However, the relevant mechanisms are unknown. Here, we investigate the effects of aspirin on expression of hepcidin and iron regulatory protein 1 (IRP1), phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and P65 (nuclear factor-κB), and the production of nitric oxide (NO) in BV-2 microglial cells treated with and without LPS...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27980776/macrophagic-control-of-the-response-to-uropathogenic-e-coli-infection-by-regulation-of-iron-retention-in-an-il-6-dependent-manner
#16
Nana Owusu-Boaitey, Kyle A Bauckman, Tingxuan Zhang, Indira U Mysorekar
INTRODUCTION: Uropathogenic Escherichia coli (UPEC), the causative agent of over 85% of urinary tract infections (UTIs), elaborate a number of siderophores to chelate iron from the host. On the other hand, the host immune imperative is to limit the availability of iron to the bacteria. Little is known regarding the mechanisms underlying this host-iron-UPEC interaction. Our objective was to determine whether macrophages, in response to UPEC infection, retain extracellular siderophore-bound and free iron, thus limiting the ability of UPEC to access iron...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27980120/production-and-characterization-of-functional-recombinant-hybrid-heteropolymers-of-camel-hepcidin-and-human-ferritin-h-and-l-chains
#17
Mohamed Boumaiza, Fernando Carmona, Maura Poli, Michela Asperti, Alessandra Gianoncelli, Michela Bertuzzi, Paola Ruzzenenti, Paolo Arosio, Mohamed Nejib Marzouki
Hepcidin is a liver-synthesized hormone that plays a central role in the regulation of systemic iron homeostasis. To produce a new tool for its functional properties the cDNA coding for camel hepcidin-25 was cloned at the 5'end of human FTH sequence into the pASK-IBA43plus vector for expression in Escherichiacoli The recombinant fusion hepcidin-ferritin-H subunit was isolated as an insoluble iron-containing protein. When alone it did not refold in a 24-mer ferritin molecule, but it did when renatured together with H- or L-ferritin chains...
December 15, 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27897970/an-essential-cell-autonomous-role-for-hepcidin-in-cardiac-iron-homeostasis
#18
Samira Lakhal-Littleton, Magda Wolna, Yu Jin Chung, Helen C Christian, Lisa C Heather, Marcella Brescia, Vicky Ball, Rebeca Diaz, Ana Santos, Daniel Biggs, Kieran Clarke, Benjamin Davies, Peter A Robbins
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27896572/identification-of-novel-mutations-in-hfe-hfe2-tfr2-and-slc40a1-genes-in-chinese-patients-affected-by-hereditary-hemochromatosis
#19
Yongwei Wang, Yali Du, Gang Liu, Shanshan Guo, Bo Hou, Xianyong Jiang, Bing Han, Yanzhong Chang, Guangjun Nie
Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups...
November 28, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27890361/iron-dysregulation-in-beta-thalassemia
#20
REVIEW
Kamonlak Leecharoenkiat, Pathrapol Lithanatudom, Wannapa Sornjai, Duncan R Smith
Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide. Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron. The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis. Ferroportin is the sole cellular iron export protein, and its expression is regulated transcriptionally, post-transcriptionally and post-translationally. Hepcidin, a hormone produced by liver cells, post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes...
November 2016: Asian Pacific Journal of Tropical Medicine
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