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Ferroportin

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https://www.readbyqxmd.com/read/28780484/expression-of-hepcidin-and-ferroportin-in-full-term-placenta-of-pregnant-cows
#1
Sante Roperto, Valeria Russo, Chiara Urraro, Anna Cutarelli, Antonella Perillo, Francesca De Falco, Franco Roperto
Hepcidin (HEP) and ferroportin (FPN) play a central role in systemic iron homeostasis. The HEP/FPN axis controls both extracellular iron concentration and total body iron levels. HEP is synthesized mainly by hepatocytes and controls the absorption of dietary iron and the distribution of iron to the various cell types; its synthesis is regulated by both iron and innate immunity. FPN is a membrane protein and the major exporter of iron from mammalian cells, including iron recycling macrophages, iron absorbing duodenal enterocytes, and iron storing hepatocytes...
July 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/28775066/the-interplay-between-iron-and-oxygen-homeostasis-with-a-particular-focus-on-the-heart
#2
Samira Lakhal-Littleton, Peter A Robbins
Iron is subject to tight homeostatic control in mammals. At the systemic level, iron homeostasis is controlled by the liver-derived hormone hepcidin acting on its target ferroportin in the gut, spleen and liver, which form the sites of iron uptake, recycling and storage, respectively. At the cellular level, iron homeostasis is dependent on the iron regulatory proteins IRP1/IRP2. Unique chemical properties of iron underpin its importance in biochemical reactions involving oxygen. As such, it is not surprising that there are reciprocal regulatory links between iron and oxygen homeostasis, operating both at the systemic and cellular levels...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28774878/the-actin-binding-protein-profilin-2-is-a-novel-regulator-of-iron-homeostasis
#3
Sara Luscieti, Bruno Galy, Lucia Gutierrez, Michael Reinke, Jorge Couso, Maya Shvartsman, Antonio Di Pascale, Walter Witke, Matthias W Hentze, Pietro Pilo Boyl, Mayka Sanchez
Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target mRNAs. We identified the profilin2 (Pfn2) mRNA, which encodes an actin binding protein involved in endocytosis and neurotransmitters release, as a novel IRP-interacting transcript and studied its role in iron metabolism. Combination of EMSA experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28762519/pathological-changes-in-sertoli-cells-and-dysregulation-of-divalent-metal-transporter-1-with-iron-responsive-element-in%C3%A2-the-testes-of-idiopathic-azoospermia-patients
#4
T Jing, P Wang, Y Liu, J Zhao, X Niu, X Wang
Iron is essential for rapidly dividing spermatocytes during normal mammalian spermatogenesis. Decreased transferrin and transferrin receptor levels were observed in seminal plasma from idiopathic azoospermia (IA) patients, suggesting disturbed iron metabolism in IA testes. However, how Sertoli cells (SCs) contribute to the iron homoeostasis in IA is still unclear. In this study, we analysed 30 IA and 30 age-matched obstructive azoospermia (OA) patients undergoing testicular sperm aspiration (TESA). SCs hyperplasia was indicated by higher SC density and Ki-67 labelling index in the IA TESA specimens...
August 1, 2017: Andrologia
https://www.readbyqxmd.com/read/28760901/synthetic-porcine-hepcidin-exerts-opposite-roles-in-escherichia-coli-and-salmonella-infections
#5
Dan Liu, Zhen-Shun Gan, Wan Ma, Hai-Tao Xiong, Yun-Qing Li, Yi-Zhen Wang, Hua-Hua Du
Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and infection threat and orchestrate a series of host protective responses. There have been several studies investigating the antimicrobial role of hepcidin but controversial. Here, we aim to examine the role of hepcidin in bacterial adherence and invasion in vitro We found that porcine hepcidin could decrease the amount of extracellular pathogen enterotoxigenic Escherichia coli (ETEC) K88 that adhered to cells by aggregating bacteria...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28737806/whole-blood-fe-isotopic-signature-in-a-sub-saharan-african-population
#6
Justin C Cikomola, María R Flórez, Marta Costas-Rodríguez, Yulia Anoshkina, Karl Vandepoele, Philippe B Katchunga, Antoine S Kishabongo, Marijn M Speeckaert, Frank Vanhaecke, Joris R Delanghe
The Fe isotopic composition of an individual's whole blood has recently been shown to be an interesting clinical indicator of Fe status. The present study aimed to evaluate the influence of several endemic characteristics of a representative population of the South Kivu province, an Fe-rich volcanic African region, on the whole blood Fe isotopic composition. Both diabetes mellitus and the ferroportin Q248H mutation are very common in Africa and are strongly associated with impairments in Fe metabolism. Fe isotopic analysis of whole blood samples was carried out using multi-collector inductively coupled plasma-mass spectrometry (after chromatographic isolation of the target element)...
August 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28704474/dietary-hemoglobin-rescues-young-piglets-from-severe-iron-deficiency-anemia-duodenal-expression-profile-of-genes-involved-in-heme-iron-absorption
#7
Robert Staroń, Paweł Lipiński, Małgorzata Lenartowicz, Aleksandra Bednarz, Anna Gajowiak, Ewa Smuda, Wojciech Krzeptowski, Marek Pieszka, Tamara Korolonek, Iqbal Hamza, Dorine W Swinkels, Rachel P L Van Swelm, Rafał R Starzyński
Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status...
2017: PloS One
https://www.readbyqxmd.com/read/28697999/the-protective-role-of-tet2-in-erythroid-iron-homeostasis-against-oxidative-stress-and-erythropoiesis
#8
Shanqi Guo, Xingkang Jiang, Yuanyuan Wang, Liwei Chen, Huzi Li, Xiaojiang Li, Yingjie Jia
Although previous studies suggested that stress erythropoiesis and iron metabolism regulate each other to increase iron availability for hemoglobin synthesis, the molecular bases determining its different traits remain elusive. In addition, global DNA demethylation has been reported during mouse erythropoiesis in vivo. However, the understanding of iron-related genes through DNA demethylation under stress erythropoiesis is largely unknown. In the current study, we found disordered iron homeostasis and misregulated hepcidin-ferroportin axis under stress erythropoiesis...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28694024/iron-metabolism-state-of-the-art
#9
R Daher, Z Karim
Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1...
July 7, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28691023/iron-homeostasis-in-tissues-is-affected-during-persistent-chlamydia-pneumoniae-infection-in-mice
#10
Marie Edvinsson, Jonas Tallkvist, Christina Nyström-Rosander, Nils-Gunnar Ilbäck
Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe changes in tissues during persistent infection or affects bacterial replication in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days. Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of infection/inflammation, increased on day 4 and tended to increase again on day 40...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28684130/indoleamine-2-3-dioxygenase-and-iron-are-required-for-mycobacterium-leprae-survival
#11
Mayara Garcia de Mattos Barbosa, Rhana Berto da Silva Prata, Priscila Ribeiro Andrade, Helen Ferreira, Bruno Jorge de Andrade Silva, Jéssica Araújo da Paixão de Oliveira, Tayná Quintella Assis, Thiago Gomes de Toledo-Pinto, Ohanna Cavalcanti de Lima Bezerra, José Augusto da Costa Nery, Patricia Sammarco Rosa, Marcelo Torres Bozza, Flávio Alves Lara, Milton Ozório Moraes, Veronica Schmitz, Euzenir Nunes Sarno, Roberta Olmo Pinheiro
Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells...
July 3, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28681497/the-dynamics-of-hepcidin-ferroportin-internalization-and-consequences-of-a-novel-ferroportin-disease-mutation
#12
Daniel F Wallace, Cameron J McDonald, Lesa Ostini, David Iser, Annabel Tuckfield, V Nathan Subramaniam
The hepcidin-ferroportin axis underlies the pathophysiology of many iron-associated disorders and is a key target for the development of therapeutics for treating iron-associated disorders. The aims of this study were to investigate the dynamics of hepcidin-mediated ferroportin internalization and the consequences of a novel disease-causing mutation on ferroportin function. Specific reagents for ferroportin are limited; we developed and characterized antibodies against the largest extracellular loop of ferroportin and developed a novel cell-based assay for studying hepcidin-ferroportin function...
July 6, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28672025/interleukin-6-regulates-iron-related-proteins-through-c-jun-n-terminal-kinase-activation-in-bv2-microglial-cell-lines
#13
Shida Zhou, Xinxing Du, Junxia Xie, Jun Wang
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) and subsequent DA depletion in the striatum. Microglia activation and nigral iron accumulation play important roles in the pathogenesis of PD. Activated microglia show increased iron deposits. However, the relationship between microglia activation and iron accumulation remains unclear. In the present study, we aimed to determine how iron levels affect interleukin-6 (IL-6) synthesis, and the effect of IL-6 on cellular iron metabolism in BV2 microglial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28671021/upregulation-of-transferrin-receptor-1-induces-cholangiocarcinoma-progression-via-induction-of-labile-iron-pool
#14
Wassana Jamnongkan, Raynoo Thanan, Anchalee Techasen, Nisana Namwat, Watcharin Loilome, Piyapharom Intarawichian, Attapol Titapun, Puangrat Yongvanit
Labile iron pool is a cellular source of ions available for Fenton reactions resulting in oxidative stress. Living organisms avoid an excess of free irons by a tight control of iron homeostasis. We investigated the altered expression of iron regulatory proteins and iron discrimination in the development of liver fluke-associated cholangiocarcinoma. Additionally, the levels of labile iron pool and the functions of transferrin receptor-1 on cholangiocarcinoma development were also identified. Iron deposition was determined using the Prussian blue staining method in human cholangiocarcinoma tissues...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28669019/altered-expression-of-intestinal-duodenal-cytochrome-b-and-divalent-metal-transporter-1-might-be-associated-with-cardio-renal-anemia-syndrome
#15
Yoshiro Naito, Hisashi Sawada, Makiko Oboshi, Keisuke Okuno, Seiki Yasumura, Yoshitaka Okuhara, Akiyo Eguchi, Koichi Nishimura, Yuko Soyama, Masanori Asakura, Masaharu Ishihara, Takeshi Tsujino, Tohru Masuyama
The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome...
July 1, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28663751/lactoferrin-efficiently-counteracts-the-inflammation-induced-changes-of-the-iron-homeostasis-system-in-macrophages
#16
Antimo Cutone, Luigi Rosa, Maria Stefania Lepanto, Mellani Jinnett Scotti, Francesca Berlutti, Maria Carmela Bonaccorsi di Patti, Giovanni Musci, Piera Valenti
Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28659169/the-novel-compound-pbt434-prevents-iron-mediated-neurodegeneration-and-alpha-synuclein-toxicity-in-multiple-models-of-parkinson-s-disease
#17
David I Finkelstein, Jessica L Billings, Paul A Adlard, Scott Ayton, Amelia Sedjahtera, Colin L Masters, Simon Wilkins, David M Shackleford, Susan A Charman, Wojciech Bal, Izabela A Zawisza, Ewa Kurowska, Andrew L Gundlach, Sheri Ma, Ashley I Bush, Dominic J Hare, Philip A Doble, Simon Crawford, Elisabeth Cl Gautier, Jack Parsons, Penny Huggins, Kevin J Barnham, Robert A Cherny
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions...
June 28, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28655775/the-iron-chaperone-poly-rc-binding-protein-2-forms-a-metabolon-with-the-heme-oxygenase-1-cytochrome-p450-reductase-complex-for-heme-catabolism-and-iron-transfer
#18
Izumi Yanatori, Des R Richardson, Shinya Toyokuni, Fumio Kishi
Mammals incorporate a major proportion of absorbed iron as heme, which is catabolized by the heme oxygenase 1 (HO1)-NADPH-cytochrome P450 reductase (CPR) complex into biliverdin, carbon monoxide, and ferrous iron. Moreover, intestinal iron is incorporated as ferrous iron, which is transported via the iron importer, divalent metal transporter 1 (DMT1). Recently, we demonstrated that the iron chaperone poly(rC)-binding protein 2 (PCBP2) can directly receive ferrous iron from DMT1 or transfer iron to the iron exporter, ferroportin 1...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28652306/hepcidin-in-dependent-mechanisms-of-iron-metabolism-regulation-during-infection-by-listeria-and-salmonella
#19
Ana C Moreira, João V Neves, Tânia Silva, Patrícia Oliveira, Maria S Gomes, Pedro N Rodrigues
During bacterial infection, the pathogenic agent and the host battle for iron, due to its importance for fundamental cellular processes. However, iron redistribution and sequestration during infection can culminate in anemia. Although hepcidin has been recognized as the key regulator of iron metabolism, in some infections its levels remain unaffected, suggesting the involvement of other players on iron metabolism deregulation. In this work, we use a mouse model to elucidate the main cellular and molecular mechanisms that lead to iron re-distribution during infection with two different pathogens: Listeria monocytogenes and Salmonella Typhimurium...
June 26, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28651003/iron-elevation-and-adipose-tissue-remodeling-in-the-epididymal-depot-of-a-mouse-model-of-polygenic-obesity
#20
Xiaoya Ma, Vinh T Pham, Hiroyuki Mori, Ormond A MacDougald, Yatrik M Shah, Peter F Bodary
BACKGROUND: Iron dysregulation is a potential contributor to the pathology of obesity-related metabolic complications. KK/HIJ (KK) mice, a polygenic obese mouse model, have elevated serum iron levels. A subset of KK male mice display a bronzing of epididymal adipose tissue (eAT) associated with >100-fold (p<0.001) higher iron concentration. METHODS: To further phenotype and characterize the adipose tissue iron overload, 27 male KK mice were evaluated. 14 had bronzing eAT and 13 had normal appearing eAT...
2017: PloS One
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