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Ferroportin

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https://www.readbyqxmd.com/read/29659961/multi-copper-ferroxidase-deficient-mice-have-increased-brain-iron-concentrations-and-learning-and-memory-deficits
#1
Jiashuo Zheng, Ruiwei Jiang, Min Chen, Zaitunamu Maimaitiming, Junzhuo Wang, Gregory J Anderson, Chris D Vulpe, Joshua L Dunaief, Huijun Chen
Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice...
April 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29659573/whole-body-iron-transport-and-metabolism-mechanistic-multi-scale-model-to-improve-treatment-of-anemia-in-chronic-kidney-disease
#2
Joydeep Sarkar, Alka A Potdar, Gerald M Saidel
Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of erythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during disease (e...
April 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29624734/predominant-role-of-microglia-in-brain-iron-retention-in-sanfilippo-syndrome-a-pediatric-neurodegenerative-disease
#3
Vincent Puy, Walaa Darwiche, Stéphanie Trudel, Cathy Gomila, Christelle Lony, Laurent Puy, Thibaud Lefebvre, Sandrine Vitry, Agnès Boullier, Zoubida Karim, Jérôme Ausseil
Neuroinflammation and iron accumulation are hallmarks of a variety of adult neurodegenerative diseases. In Sanfilippo syndrome (mucopolysaccharidosis type III, MPSIII, a pediatric neurodegenerative disease that shares some features with adult neurodegenerative diseases), the progressive accumulation of heparan sulfate oligosaccharides (HSOs) induces microglia and astrocytes to produce pro-inflammatory cytokines leading to severe neuroinflammation. The objectives of the present study were (1) to measure the local iron concentration and to assess iron metabolism in the brain of a MPSIIIB murine model and (2) to identify the brain cells involved in this accumulation...
April 6, 2018: Glia
https://www.readbyqxmd.com/read/29620054/haemochromatosis
#4
REVIEW
Pierre Brissot, Antonello Pietrangelo, Paul C Adams, Barbara de Graaff, Christine E McLaren, Olivier Loréal
Haemochromatosis is defined as systemic iron overload of genetic origin, caused by a reduction in the concentration of the iron regulatory hormone hepcidin, or a reduction in hepcidin-ferroportin binding. Hepcidin regulates the activity of ferroportin, which is the only identified cellular iron exporter. The most common form of haemochromatosis is due to homozygous mutations (specifically, the C282Y mutation) in HFE, which encodes hereditary haemochromatosis protein. Non-HFE forms of haemochromatosis due to mutations in HAMP, HJV or TFR2 are much rarer...
April 5, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29599243/erythrocytic-ferroportin-reduces-intracellular-iron-accumulation-hemolysis-and-malaria-risk
#5
De-Liang Zhang, Jian Wu, Binal N Shah, Katja C Greutélaers, Manik C Ghosh, Hayden Ollivierre, Xin-Zhuan Su, Philip E Thuma, George Bedu-Addo, Frank P Mockenhaupt, Victor R Gordeuk, Tracey A Rouault
Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice...
March 30, 2018: Science
https://www.readbyqxmd.com/read/29575577/smad7-deficiency-decreases-iron-and-haemoglobin-through-hepcidin-up-regulation-by-multilayer-compensatory-mechanisms
#6
Peng An, Hao Wang, Qian Wu, Jiaming Wang, Zhidan Xia, Xuyan He, Xinhui Wang, Yan Chen, Junxia Min, Fudi Wang
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte-specific Smad7 knockout mice (Smad7Alb/Alb ), which showed decreased serum iron, tissue iron, haemoglobin concentration, up-regulated hepcidin and increased phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29562821/high-dose-deferoxamine-treatment-disrupts-intracellular-iron-homeostasis-reduces-growth-and-induces-apoptosis-in-metastatic-and-nonmetastatic-breast-cancer-cell-lines
#7
Khuloud Bajbouj, Jasmin Shafarin, Mawieh Hamad
Mounting evidence suggest that iron overload enhances cancer growth and metastasis; hence, iron chelation is being increasingly used as part of the treatment regimen in patients with cancer. Now whether iron chelation depletes intracellular iron and/or disrupts intracellular iron homeostasis is yet to be fully addressed. MCF-7 and MDA-MB-231 breast cancer cells treated with increasing concentrations of the iron chelator deferoxamine were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, cell viability, growth potential, and apoptosis at different time points following treatment...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29552621/ferroportin-expression-in-adipocytes-does-not-contribute-to-iron-homeostasis-or-metabolic-responses-to-a-high-calorie-diet
#8
Laurence Britton, Lesley-Anne Jaskowski, Kim Bridle, Eriza Secondes, Daniel Wallace, Nishreen Santrampurwala, Janske Reiling, Gregory Miller, Salvatore Mangiafico, Sofianos Andrikopoulos, V Nathan Subramaniam, Darrell Crawford
Background & Aims: Iron has an increasingly recognized role in the regulation of adipose tissue function, including the expression of adipokines involved in the pathogenesis of nonalcoholic fatty liver disease. The cellular iron exporter, ferroportin, has been proposed as being a key determinant of adipocyte iron homeostasis. Methods: We studied an adipocyte-specific ferroportin ( Fpn1 ) knockout mouse model, using an Adipoq -Cre recombinase driven Fpn1 deletion and fed mice according to the fast food diet model of nonalcoholic steatohepatitis...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29532452/hepcidin-an-iron-regulatory-hormone-of-innate-immunity-is-differentially-expressed-in-premature-fetuses-with-early-onset-neonatal-sepsis
#9
Sammy M Tabbah, Catalin S Buhimschi, Katherine Rodewald-Millen, Christopher R Pierson, Vineet Bhandari, Philip Samuels, Irina A Buhimschi
OBJECTIVE:  Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN:  Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS ( n  = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS ( n  = 51, GA 26 ± 1 weeks)...
February 2, 2018: American Journal of Perinatology
https://www.readbyqxmd.com/read/29518107/gene-gene-interactions-among-coding-genes-of-iron-homeostasis-proteins-and-apoe-alleles-in-cognitive-impairment-diseases
#10
Veronica Tisato, Giovanni Zuliani, Marco Vigliano, Giovanna Longo, Eugenia Franchini, Paola Secchiero, Giorgio Zauli, Elvezia Maria Paraboschi, Ajay Vikram Singh, Maria Luisa Serino, Beatrice Ortolani, Amedeo Zurlo, Cristina Bosi, Antonio Greco, Davide Seripa, Rosanna Asselta, Donato Gemmati
Cognitive impairments of different aetiology share alterations in iron and lipid homeostasis with mutual relationships. Since iron and cholesterol accumulation impact on neurodegenerative disease, the associated gene variants are appealing candidate targets for risk and disease progression assessment. In this light, we explored the role of common single nucleotide polymorphisms (SNPs) in the main iron homeostasis genes and in the main lipoprotein transporter gene (APOE) in a cohort of 765 patients with dementia of different origin: Alzheimer's disease (AD) n = 276; vascular dementia (VaD), n = 255; mild cognitive impairment (MCI), n = 234; and in normal controls (n = 1086)...
2018: PloS One
https://www.readbyqxmd.com/read/29478228/high-dietary-iron-differentially-influences-the-iron-distribution-in-the-livers-and-the-spleens-of-laying-hens-after-salmonella-typhimurium-infection
#11
Shiping Bai, Keying Zhang, Xuemei Ding, Jianping Wang, Qiufeng Zeng, Huanwei Peng, Yue Xuan, Zuowei Su, Jie Bai
Salmonella and the host battle for iron (Fe), due to its importance for fundamental cellular processes. To investigate Fe redistribution of Salmonella-infected hens and the effects of high dietary Fe on it, Salmonella-free hens were randomly assigned to 1 of 4 treatments in 2 (two dietary Fe level) × 2 (Salmonella-inoculation or -noninoculation) factorial assignment. After feeding a basal diet supplemented with 60 (adequate, control) or 300 mg Fe/kg (high-Fe) for 4 weeks, 59-week-old Salmonella-free hens were orally inoculated with 5 × 107 colony-forming units of Salmonella Typhimurium (infection) or PBS (vehicle)...
February 24, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29472371/how-does-hepcidin-hinder-ferroportin-activity
#12
De-Liang Zhang, Tracey A Rouault
No abstract text is available yet for this article.
February 22, 2018: Blood
https://www.readbyqxmd.com/read/29470856/leishmania-donovani-inhibits-ferroportin-translation-by-modulating-fbxl5-irp2-axis-for-its-growth-within-host-macrophages
#13
Nupur Kanti Das, Sandhya Sandhya, G Vishnu Vivek, Rajiv Kumar, Amit Kumar Singh, Saswat Kumar Bal, Sanju Kumari, Chinmay K Mukhopadhyay
Hepcidin mediated ferroportin (Fpn) degradation in macrophages is a well adopted strategy to limit iron availability towards invading pathogens. Leishmania donovani (LD), a protozoan parasite, resides within macrophage and competes with host for availing iron. Using in vitro and in vivo model of infection we reveal that LD decreases Fpn abundance in host macrophages by hepcidin independent mechanism. Unaffected level of Fpn-FLAG in LD infected J774 macrophage confirms that Fpn down-regulation is not due its degradation...
February 22, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29453656/the-ferroportin-ceruloplasmin-system-and-the-mammalian-iron-homeostasis-machine-regulatory-pathways-and-the-role-of-lactoferrin
#14
Maria Carmela Bonaccorsi di Patti, Antimo Cutone, Fabio Polticelli, Luigi Rosa, Maria Stefania Lepanto, Piera Valenti, Giovanni Musci
In the last 20 years, several new genes and proteins involved in iron metabolism in eukaryotes, particularly related to pathological states both in animal models and in humans have been identified, and we are now starting to unveil at the molecular level the mechanisms of iron absorption, the regulation of iron transport and the homeostatic balancing processes. In this review, we will briefly outline the general scheme of iron metabolism in humans and then focus our attention on the cellular iron export system formed by the permease ferroportin and the ferroxidase ceruloplasmin...
February 16, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29452354/alpha-synuclein-inhibits-snx3-retromer-mediated-retrograde-recycling-of-iron-transporters-in-s-cerevisiae-and-c-elegans-models-of-parkinson-s-disease
#15
Dhaval Patel, Chuan Xu, Sureshbabu Nagarajan, Zhengchang Liu, Wayne O Hemphill, Runhua Shi, Vladimir N Uversky, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We probed the role of alpha-synuclein (α-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound multicopper ferroxidase, whose ferroxidase domain is orthologous to human ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then channel through the Ftr1 permease into the cell. When the concentration of external iron is low (< 1 µM), Fet3/Ftr1 is maintained on the plasma membrane by retrograde endocytic-recycling; whereas, when the concentration of external iron is high (> 10 µM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for degradation...
February 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29451472/hepcidin-and-proinflammatory-markers-in-children-with-chronic-kidney-disease-a-case-control-study
#16
Kamal Kumar Goyal, Abhijeet Saha, Puneet Kaur Sahi, Manpreet Kaur, Nand Kishore Dubey, Parul Goyal, Ashish Dutt Upadhayay
BACKGROUND: Hepcidin is the main regulator of hepcidin-ferroportin axis and is elevated in children with chronic kidney disease (CKD). Anemia of CKD and its relation to hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in iron- and erythropoietin (EPO)-naïve, non-dialyzed children with CKD is under-studied. MATERIALS AND METHODS: This case-control study aimed to study the levels of hepcidin and other proinflammatory markers (IL-6, TNF-α, hs-CRP) and their relation with anemia in iron- and erythropoietin-naïve, non-dialysis CKD (stage 3 - 5) patients...
February 16, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29436589/ferroptosis-is-associated-with-oxygen-glucose-deprivation-reoxygenation-induced-sertoli-cell-death
#17
Li Li, Yu Hao, Yu Zhao, Huijuan Wang, Xiujun Zhao, Yan Jiang, Fulu Gao
Sertoli cell death contributes to spermatogenesis impairment, which is associated with male infertility. Testicular ischemia‑reperfusion (I/R) injury induces the cell death of germ cells and Sertoli cells, whereas inhibition of cell death ameliorates acute testicular I/R damage. The aim of the present study was to investigate the mechanism of I/R stress-induced cell death in TM4 cells. Oxygen‑glucose deprivation and reoxygenation (OGD/R) was demonstrated to induce I/R injury and cell death in TM4 cells...
February 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29430595/the-c19s-substitution-enhances-the-stability-of-hepcidin-while-conserving-its-biological-activity
#18
Edina Pandur, Zsuzsanna Fekete, Kitti Tamási, László Grama, Edit Varga, Katalin Sipos
Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level through its interaction with iron exporter ferroportin. Thus, hepcidin agonists provide a promising opportunity in the treatment of iron disorders caused by lacking or decreased hepcidin expression. We investigated the importance of each of the eight highly conserved cysteines for the biological activity of hepcidin. Eight cysteine mutants were created with site directed mutagenesis. The binding ability of these hepcidin mutants to the hepcidin receptor ferroportin was determined using bacterial two-hybrid system and WRL68 human hepatic cells...
February 12, 2018: Protein Journal
https://www.readbyqxmd.com/read/29410496/identification-of-a-novel-na-coupled-fe-3-citrate-transport-system-distinct-from-mammalian-indy-for-uptake-of-citrate-in-mammalian-cells
#19
Jiro Ogura, Ellappan Babu, Seiji Miyauchi, Sabarish Ramachandran, Elizebeta Nemeth, Yangzom D Bhutia, Vadivel Ganapathy
NaCT is a Na + -coupled transporter for citrate expressed in hepatocytes and neurons. It is the mammalian ortholog of INDY (I'm Not Dead Yet), a transporter which modifies lifespan in Drosophila. Here we describe a hitherto unknown transport system for citrate in mammalian cells. When liver and mammary epithelial cells were pretreated with the iron supplement ferric ammonium citrate (FAC), uptake of citrate increased >10-fold. Iron chelators abrogated the stimulation of citrate uptake in FAC-treated cells...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29407213/iron-released-from-reactive-microglia-by-noggin-improves-myelin-repair-in-the-ischemic-brain
#20
Jin A Shin, Yul A Kim, Hye Won Kim, Hee-Sun Kim, Kyung-Eun Lee, Jihee Lee Kang, Eun-Mi Park
We previously reported that the bone morphogenetic protein (BMP) antagonist, noggin, improved the repair process with an increase in the reactive microglia/macrophage population in the ischemic brain. Since BMP plays a role in intracellular iron homeostasis via the hepcidin/ferroportin axis, and iron is required for myelination, this study was aimed to determine whether noggin affected iron status and remyelination in the brain following ischemic stroke. We further examined the effect of blocking the BMP/hepcidin pathway on reactive microglia (BV2) and myelination of oligodendroglial cells (MO3...
January 30, 2018: Neuropharmacology
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