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Ferroportin

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https://www.readbyqxmd.com/read/29453656/the-ferroportin-ceruloplasmin-system-and-the-mammalian-iron-homeostasis-machine-regulatory-pathways-and-the-role-of-lactoferrin
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/29406047/iron-enhances-hepatic-fibrogenesis-and-activates-transforming-growth-factor-%C3%AE-signaling-in-murine-hepatic-stellate-cells
#8
Kosha J Mehta, Jason D Coombes, Marco Briones-Orta, Paul P Manka, Roger Williams, Vinood B Patel, Wing-Kin Syn
BACKGROUND: Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC). MATERIALS AND METHODS: We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.005-5g/L) for 24 hours, with or without the iron chelator deferoxamine (10µM). Gene expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by quantitative real time-polymerase chain reaction, whereas TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated by immunofluorescence, Western blot and enzyme-linked immunosorbent assay...
February 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29377263/the-%C3%AE-1-adrenergic-receptor-is-involved-in-hepcidin-upregulation-induced-by-adrenaline-and-norepinephrine-via-the-stat3-pathway
#9
Wei-Na Kong, Yanmei Cui, Yu-Jian Fu, Yuhua Lei, Yunzhe Ci, Yongping Bao, Shuqiang Zhao, Lide Xie, Yan-Zhong Chang, Shu-E Zhao
Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1-adrenergic receptor agonist), prazosin (PZ, α1-adrenergic receptor antagonist), and/or propranolol (Pro, β-adrenergic receptor antagonist)...
January 29, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29373036/timp3-deficiency-exacerbates-iron-overload-mediated-cardiomyopathy-and-liver-disease
#10
Pavel Zhabyeyev, Subhash K Das, Ratnadeep Basu, Mengcheng Shen, Vaibhav B Patel, Zamaneh Kassiri, Gavin Y Oudit
Chronic iron-overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron-overload. We investigated the role of tissue inhibitor of metalloproteinase-3 (TIMP3) in iron-overload mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wildtype (WT) mice to 12 weeks of chronic iron-overload. While iron-overload in the WT group developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29343241/clinical-features-and-dysfunctions-of-iron-metabolism-in-parkinson-disease-patients-with-hyper-echogenicity-in-substantia-nigra-a-cross-sectional-study
#11
Shu-Yang Yu, Chen-Jie Cao, Li-Jun Zuo, Ze-Jie Chen, Teng-Hong Lian, Fang Wang, Yang Hu, Ying-Shan Piao, Li-Xia Li, Peng Guo, Li Liu, Qiu-Jin Yu, Rui-Dan Wang, Piu Chan, Sheng-di Chen, Xiao-Min Wang, Wei Zhang
BACKGROUND: Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. METHODS: PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group...
January 17, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29329289/burkholderia-pseudomallei-modulates-host-iron-homeostasis-to-facilitate-iron-availability-and-intracellular-survival
#12
Imke H E Schmidt, Claudia Gildhorn, Martha A L Böning, Vera A Kulow, Ivo Steinmetz, Antje Bast
BACKGROUND: The control over iron homeostasis is critical in host-pathogen-interaction. Iron plays not only multiple roles for bacterial growth and pathogenicity, but also for modulation of innate immune responses. Hepcidin is a key regulator of host iron metabolism triggering degradation of the iron exporter ferroportin. Although iron overload in humans is known to increase susceptibility to Burkholderia pseudomallei, it is unclear how the pathogen competes with the host for the metal during infection...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29305416/involvement-of-hepcidin-in-iron-metabolism-dysregulation-in-gaucher-disease
#13
Thibaud Lefebvre, Niloofar Reihani, Raed Daher, Thierry Billette de Villemeur, Nadia Belmatoug, Christian Rose, Yves Colin-Aronovicz, Hervé Puy, Caroline Le Van Kim, Mélanie Franco, Zoubida Karim
Gaucher disease is an inherited deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in tissues such as the spleen, liver, and bone marrow. The resulting lipid-laden macrophages lead to the appearance of Gaucher cells. Anemia associated with an unexplained hyperferritinemia is a frequent finding in Gaucher disease, but whether this pathogenesis is related to an iron metabolism disorder has remained unclear. To investigate this issue, we explored the iron status of a large cohort of 90 type I Gaucher disease patients, including 66 patients treated with enzyme replacement therapy...
January 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29296776/intestinal-hephaestin-potentiates-iron-absorption-in-weanling-adult-and-pregnant-mice-under-physiological-conditions
#14
Caglar Doguer, Jung-Heun Ha, Sukru Gulec, Chris D Vulpe, Gregory J Anderson, James F Collins
Regulation of intestinal iron absorption is crucial to maintain body iron levels because humans have no regulated iron-excretory system. Elucidating molecular events that mediate intestinal iron transport is thus important for the development of therapeutic approaches to modify iron absorption in pathological states. The process of iron uptake into duodenal enterocytes is relatively well understood, but less is known about the functional coupling between the iron exporter ferroportin 1 and the basolateral membrane iron oxidase hephaestin (Heph)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29247214/dysregulation-of-iron-metabolism-in-cholangiocarcinoma-stem-like-cells
#15
Chiara Raggi, Elena Gammella, Margherita Correnti, Paolo Buratti, Elisa Forti, Jesper B Andersen, Gianfranco Alpini, Shannon Glaser, Domenico Alvaro, Pietro Invernizzi, Gaetano Cairo, Stefania Recalcati
Cholangiocarcinoma (CCA) is a devastating liver tumour arising from malignant transformation of bile duct epithelial cells. Cancer stem cells (CSC) are a subset of tumour cells endowed with stem-like properties, which play a role in tumour initiation, recurrence and metastasis. In appropriate conditions, CSC form 3D spheres (SPH), which retain stem-like tumour-initiating features. Here, we found different expression of iron proteins indicating increased iron content, oxidative stress and higher expression of CSC markers in CCA-SPH compared to tumour cells growing as monolayers...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29237594/structure-function-analysis-of-ferroportin-defines-the-binding-site-and-an-alternative-mechanism-of-action-of-hepcidin
#16
Sharraya Aschemeyer, Bo Qiao, Deborah Stefanova, Erika V Valore, Albert C Sek, T Alex Ruwe, Kyle R Vieth, Grace Jung, Carla Casu, Stefano Rivella, Mika Jormakka, Bryan Mackenzie, Tomas Ganz, Elizabeta Nemeth
Non-classical Ferroportin Disease is a form of hereditary hemochromatosis caused by mutations in the iron transporter ferroportin (Fpn), resulting in parenchymal iron overload. Fpn is regulated by the hormone hepcidin, which induces Fpn endocytosis and cellular iron retention. We characterized 11 clinically-relevant and 5 nonclinical Fpn mutations using stably transfected, inducible, isogenic cell lines. All clinical mutants were functionally resistant to hepcidin as a consequence of either impaired hepcidin binding or impaired hepcidin-dependent ubiquitination despite intact hepcidin binding...
December 13, 2017: Blood
https://www.readbyqxmd.com/read/29230833/causes-of-iron-overload-in-blood-donors-a-clinical-study
#17
A H Laursen, O W Bjerrum, L Friis-Hansen, T O Hansen, J L Marott, K Magnussen
BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center...
December 12, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/29212341/scavenging-reactive-oxygen-species-production-normalizes-ferroportin-expression-and-ameliorates-cellular-and-systemic-iron-disbalances-in-hemolytic-mouse-model
#18
Naveen Kumar Tangudu, Betuel Alan, Francesca Vinchi, Katharina Woerle, Dilay Lai, Sabine Vettorazzi, Kerstin Leopold, Maja Vujic Spasic
AIMS: The release of large amounts of free heme into the circulation, overproduction of reactive oxygen species (ROS) and the activation of toll-like receptor (Tlr)-4 dependent responses are considered critical for the ability of heme to promote oxidative stress and to initiate pro-inflammatory responses, posing a serious threat to the body. A deep understanding of the consequences of heme overload on the regulation of cellular and systemic iron homeostasis is however, still lacking. RESULTS: The effects of heme on iron metabolism were studied in primary macrophages and in mouse models of acute and chronic hemolysis...
December 6, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29209212/identification-of-antibody-and-small-molecule-antagonists-of-ferroportin-hepcidin-interaction
#19
Sandra L Ross, Kaustav Biswas, James Rottman, Jennifer R Allen, Jason Long, Les P Miranda, Aaron Winters, Tara L Arvedson
The iron exporter ferroportin and its ligand, the hormone hepcidin, control fluxes of stored and recycled iron for use in a variety of essential biochemical processes. Inflammatory disorders and malignancies are often associated with high hepcidin levels, leading to ferroportin down-regulation, iron sequestration in tissue macrophages and subsequent anemia. The objective of this research was to develop reagents to characterize the expression of ferroportin, the interaction between ferroportin and hepcidin, as well as to identify novel ferroportin antagonists capable of maintaining iron export in the presence of hepcidin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29203958/role-of-catalytic-iron-and-oxidative-stress-in-nitrofen-induced-congenital-diaphragmatic-hernia-and-its-amelioration-by-saireito-tj-114
#20
Shima Hirako, Hiroyuki Tsuda, Fumiya Ito, Yasumasa Okazaki, Tasuku Hirayama, Hideko Nagasawa, Tomoko Nakano, Kenji Imai, Tomomi Kotani, Fumitaka Kikkawa, Shinya Toyokuni
Congenital diaphragmatic hernia (CDH) is a life-threatening neonatal disease that leads to lung hypoplasia and pulmonary hypertension. We recently found that maternal prenatal administration of Saireito (TJ-114) ameliorates fetal CDH in a nitrofen-induced rat model. Here, we studied the role of iron and oxidative stress in neonates of this model and in lung fibroblasts IMR90-SV in association with nitrofen and Saireito. We observed increased immunostaining of 8-hydroxy-2'-deoxyguanosine in the lungs of neonates with CDH, which was ameliorated by maternal Saireito intake...
November 2017: Journal of Clinical Biochemistry and Nutrition
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