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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
June 27, 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
#13
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
#14
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
https://www.readbyqxmd.com/read/28642463/acute-loss-of-the-hepatic-endo-lysosomal-system-in-vivo-causes-compensatory-changes-in-iron-homeostasis
#15
Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial, Martina U Muckenthaler
Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641663/-expression-changes-of-hepcidin-and-ferroportin-1-in-murine-model-of-iron-overload
#16
Jing-Wen Wang, Lu-Hong Xu, Xi Yao, Jian-Pei Fang
OBJECTIVE: To investigate the changes of hepcidin and ferropotin 1 expression in murine model of iron overload. METHODS: The murine model of iron overload was established, C57BL/6 mice were injected with iron dextran intraperitoneally (10 mg) every 3 days for 4 weeks. Blood routine, serum ferritin and pathological sections were tested at the appointed time-point respectively (before iron injection, 2 weeks and 4 weeks after treatment of iron injection). The serum hepcidin was assayed by enzyme-linked immunosorbent method...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28629515/mutual-cross-talk-between-iron-homeostasis-and-erythropoiesis
#17
Ilona Rybinska, Gaetano Cairo
Iron is necessary for physiological processes essential for the activity of all cells, but the erythropoietic compartment is a privileged iron consumer. In fact, a considerable amount of iron is daily required for hemoglobin synthesis and erythroid cell proliferation. Therefore, a tight link exists between iron metabolism and erythropoiesis. The iron needed for hemoglobin synthesis is mainly ensured by inhibiting hepcidin expression, thereby increasing both ferroportin-mediated iron export from the duodenal absorptive cells and iron release from the reticuloendothelial cells that process old and/or damaged red blood cells...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28629118/long-term-dexamethasone-exposure-down-regulates-hepatic-tfr1-and-reduces-liver-iron-concentration-in-rats
#18
Huifang Li, Shuxia Jiang, Chun Yang, Shu Yang, Bin He, Wenqiang Ma, Ruqian Zhao
Exposure to stress is known to cause hepatic iron dysregulation, but the relationship between prolonged stress and liver iron metabolism is not yet fully understood. Thirty 13-week-old female Sprague-Dawley rats were randomly divided into two groups, as follows: the control group (saline-injection) and the dexamethasone group (Dexamethasone (Dex)-injection 0.1 mg/kg/day). After the 21-day stress trial, the results showed that chronic Dex administration not only impaired serum corticosterone (p = 0.00) and interleukin-6 (IL-6) (p = 0...
June 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28622780/-iron-metabolism
#19
S Vaulont
Iron is an essential trace element ensuring many functions in the body. However, excess iron can be toxic with deleterious consequences on function and tissue integrity. The understanding of the molecular and cellular mechanisms allowing iron level to be kept at physiological concentration has greatly progressed in recent years, in particular with the identification of the iron-regulatory hormone, hepcidin and its receptor ferroportin, the sole iron exporter known to date. This discovery has improved our ability to diagnose and manage iron disorders and offered new therapeutic perspectives for an important class of human diseases...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28615456/iron-homeostasis-an-anthropocentric-perspective
#20
Richard Coffey, Tomas Ganz
The regulation of iron metabolism in biological systems centers on providing adequate iron for cellular function while limiting iron toxicity. Because mammals cannot excrete iron, mechanisms have evolved to control iron acquisition, storage, and distribution at both systemic and cellular levels. Hepcidin, the master regulator of iron homeostasis, controls iron flows into plasma through inhibition of the sole known mammalian cellular iron exporter ferroportin. Hepcidin is feedback-regulated by iron status, and strongly modulated by inflammation and erythropoietic demand...
June 14, 2017: Journal of Biological Chemistry
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