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Ferroportin

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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29196967/modern-iron-replacement-therapy-clinical-and-pathophysiological-insights
#4
REVIEW
Domenico Girelli, Sara Ugolini, Fabiana Busti, Giacomo Marchi, Annalisa Castagna
Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era...
December 1, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29177638/the-ferroxidase-hephaestin-but-not-amyloid-precursor-protein-is-required-for-ferroportin-supported-iron-efflux-in-primary-hippocampal-neurons
#5
Changyi Ji, Brittany L Steimle, Danielle K Bailey, Daniel J Kosman
Iron efflux in mammalian cells is mediated by the ferrous iron exporter ferroportin (Fpn); Fpn plasma membrane localization and function are supported by a multicopper ferroxidase and/or the soluble amyloid precursor protein (sAPP). Fpn and APP are ubiquitously expressed in all cell types in the central nervous system including neurons. In contrast, neuronal ferroxidase(s) expression has not been well characterized. Using primary cultures of hippocampal neurons, we examined the molecular mechanism of neuronal Fe efflux in detail...
November 25, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29172705/expression-of-iron-related-proteins-in-feline-and-canine-mammary-gland-reveals-unexpected-accumulation-of-iron
#6
O Marques, A Canadas, F Faria, E Oliveira, I Amorim, F Seixas, A Gama, A Lobo-da-Cunha, B Martins da Silva, G Porto, C Lopes
Dysregulation of cellular iron homeostasis in human breast cancer is reflected by the altered expression of regulatory proteins. The expressions of iron-related proteins in the mammary glands of cats and dogs have not been assessed. We evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron deposition was detected using Perls' Prussian blue staining. We found no major differences in the expression of iron-related proteins between benign and malignant mammary gland lesions in either cats or dogs; however, these species exhibited accumulation of iron in benign lesions...
November 27, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29163042/impairment-of-hepcidin-upregulation-by-lipopolysaccharide-in-the-interleukin-6-knockout-mouse-brain
#7
Fa-Li Zhang, Hui-Min Hou, Zhi-Nan Yin, Lan Chang, Fe-Mi Li, Y-J Chen, Ya Ke, Zhong-Ming Qian
To find out whether the Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the expression of hepcidin in the mouse brain in vivo, we investigated the phosphorylation of STAT3, as well as the expression of hepcidin mRNA, ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in the cortex and hippocampus of LPS-treated wild type (IL-6+/+) and IL-6 knockout (IL-6-/-) mice. We demonstrated that IL-6 knockout could significantly reduce the response of hepcidin mRNA, phospho-STAT3, Fpn1 and Ft-L protein expression to LPS treatment, in both the cortex and hippocampus of mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29158016/genetic-hemochromatosis-pathophysiology-diagnostic-and-therapeutic-management
#8
Pierre Brissot, Thibault Cavey, Martine Ropert, Pascal Guggenbuhl, Olivier Loréal
The term hemochromatosis (HC) corresponds to several diseases characterized by systemic iron overload of genetic origin and affecting both the quality of life and life expectancy. Major improvement in the knowledge of iron metabolism permits to divide these diseases into two main pathophysiological categories. For most HC forms (types 1, 2, 3 and 4B HC) iron overload is related to cellular hepcidin deprivation which causes an increase of plasma iron concentration and the appearance of plasma non-transferrin bound iron...
November 17, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29154924/characterization-of-three-novel-pathogenic-slc40a1-mutations-and-genotype-phenotype-correlations-in-7-italian-families-with-type-4-hereditary-hemochromatosis
#9
Silvia Majore, Maria Carmela Bonaccorsi di Patti, Michele Valiante, Fabio Polticelli, Andrea Cortese, Sabrina Di Bartolomeo, Carmelilia De Bernardo, Marianna De Muro, Fiorella Faienza, Francesca Clementina Radio, Paola Grammatico, Giovanni Musci
Mutations of SLC40A1 encoding ferroportin (Fpn), the unique cellular iron exporter, severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations. This disease can be classified as type 4A, better known as "ferroportin disease", which is due to "loss of function" mutations that lead to decreased iron export from cells, or as type 4B hemochromatosis, which is caused by "gain of function" mutations, conferring partial or complete resistance to hepcidin-mediated Fpn degradation...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29147463/acidic-polysaccharide-from-angelica-sinensis-reverses-anemia-of-chronic-disease-involving-the-suppression-of-inflammatory-hepcidin-and-nf-%C3%AE%C2%BAb-activation
#10
Kaiping Wang, Jun Wu, Fang Cheng, Xiao Huang, Fang Zeng, Yu Zhang
Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29136618/hepcidin-in-iron-homeostasis-diagnostic-and-therapeutic-implications-in-type-2-diabetes-mellitus-patients
#11
Sintayehu Ambachew, Belete Biadgo
The prevalence of type 2 diabetes is increasing in epidemic proportions worldwide. Evidence suggests body iron overload is frequently linked and observed in patients with type 2 diabetes. Body iron metabolism is based on iron conservation and recycling by which only a part of the daily need is replaced by duodenal absorption. The principal liver-produced peptide called hepcidin plays a fundamental role in iron metabolism. It directly binds to ferroportin, the sole iron exporter, resulting in the internalization and degradation of ferroportin...
November 15, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29135121/hepcidin-and-iron-metabolism-in-the-pathogenesis-of-prostate-cancer
#12
Feng Wang, An Liu, Ruyu Bai, Binbin Zhang, Yongsheng Jin, Wei Guo, Yi Li, Jixue Gao, Longqiang Liu
PURPOSE: To investigate the relationship between Hepcidin and iron metabolism, and cell proliferation, migration, and apoptosis in prostate cancer cells. METHODS: PC3 prostate cancer cells were cultured in vitro and divided into the control group, Hepcidin overexpression group, and Hepcidin low expression group. Prostate specific antigen (PSA) and soluble transferrin receptor (sTfR) levels were measured by ELISA. The levels of the Hepcidin receptor membrane transporter, Ferroportin, were determined by Western blot...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134618/the-mechanisms-of-systemic-iron-homeostasis-and-etiology-diagnosis-and-treatment-of-hereditary-hemochromatosis
#13
REVIEW
Hiroshi Kawabata
Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy. Classic HH type 1, which is common in Caucasians, is caused by bi-allelic mutations of HFE. Severe types of HH are caused by either bi-allelic mutations of HFE2 that encodes hemojuvelin (type 2A) or HAMP that encodes hepcidin (type 2B). HH type 3, which is of intermediate severity, is caused by bi-allelic mutations of TFR2 that encodes transferrin receptor 2...
November 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29115497/studying-hepcidin-and-related-pathways-in-osteoblasts-using-a-mouse-model-with-insulin-receptor-substrate-1%C3%A2-loss-of-function
#14
Jia Liu, Ling Qian, Linna Guo, Yunzhi Feng
Hepcidin is one of the most important proteins in iron metabolism. In the present study, its role in iron metabolism and the associated signaling pathways involved was investigated in a mouse model with insulin receptor substrate 1‑loss of function (IRS‑/‑), and osteoblasts in the iron overload condition. Protein expression levels of hepcidin, interleukin 6 (IL‑6), bone morphogenetic protein receptor 1α and ferritin demonstrated a significant increase in the liver of the IRS‑/‑ mice compared with the IRS+/‑ and IRS+/+ mice...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29101207/ferroportin-disease-pathogenesis-diagnosis-and-treatment
#15
REVIEW
Antonello Pietrangelo
Ferroportin Disease (FD) is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of the commonest causes of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In FD, loss-of-function mutations of FPN1 limit but do not impair iron export in enterocytes, but they do severely affect iron transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i...
December 2017: Haematologica
https://www.readbyqxmd.com/read/29093559/hamp1-but-not-hamp2-regulates-ferroportin-in-fish-with-two-functionally-distinct-hepcidin-types
#16
João V Neves, Miguel F Ramos, Ana C Moreira, Tânia Silva, Maria S Gomes, Pedro N S Rodrigues
Hepcidin is a small cysteine rich peptide that regulates the sole known cellular iron exporter, ferroportin, effectively controlling iron metabolism. Contrary to humans, where a single hepcidin exists, many fish have two functionally distinct hepcidin types, despite having a single ferroportin gene. This raises the question of whether ferroportin is similarly regulated by the iron regulator Hamp1 and the antimicrobial Hamp2. In sea bass (Dicentrarchus labrax), iron overload prompted a downregulation of ferroportin, associated with an upregulation of hamp1, whereas an opposite response was observed during anemia, with no changes in hamp2 in either situation...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089902/pulmonary-iron-homeostasis-in-hepcidin-knockout-mice
#17
Jean-Christophe Deschemin, Jacques R R Mathieu, Sara Zumerle, Carole Peyssonnaux, Sophie Vaulont
Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to better understand the interactions between iron-associated molecules and the hepcidin-ferroportin axis in lung iron balance, we examined lung physiology and inflammatory responses in two murine models of systemic iron-loading, either hepcidin knock-out (Hepc KO) or liver-specific hepcidin KO mice (Hepc KOliv), which do (Hepc KOliv) or do not (Hepc KO) express lung hepcidin...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29082606/increased-small-intestine-expression-of-non-heme-iron-transporters-in-morbidly-obese-patients-with-newly-diagnosed-type-2-diabetes
#18
José María Moreno-Navarrete, Amaia Rodríguez, Sara Becerril, Víctor Valentí, Javier Salvador, Gema Frühbeck, José Manuel Fernández-Real
SCOPE: To investigate intestinal markers of iron absorption in morbidly obese subjects according to glucose tolerance. METHODS AND RESULTS: Gene expression of both non-heme [SLC40A1 (ferroportin), SLC11A2] and heme iron [SLC46A1 (HCP1), HMOX1] transporters were analysed in 38 small intestine tissue samples [11 with normal glucose tolerance, 14 with glucose intolerance (GI) and 13 with newly diagnosed type 2 diabetes (T2D)]. SLC40A1 (r = 0.43, p = 0.008) and SLC11A2 (r = 0...
October 29, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29073189/effect-of-erythropoietin-administration-on-proteins-participating-in-iron-homeostasis-in-tmprss6-mutated-mask-mice
#19
Jana Frýdlová, Zuzana Rychtarčíková, Iuliia Gurieva, Martin Vokurka, Jaroslav Truksa, Jan Krijt
Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice...
2017: PloS One
https://www.readbyqxmd.com/read/29070561/development-of-iron-homeostasis-in-infants-and-young-children
#20
REVIEW
Bo Lönnerdal
Healthy, term, breastfed infants usually have adequate iron stores that, together with the small amount of iron that is contributed by breast milk, make them iron sufficient until ≥6 mo of age. The appropriate concentration of iron in infant formula to achieve iron sufficiency is more controversial. Infants who are fed formula with varying concentrations of iron generally achieve sufficiency with iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of breastfed infants at 6 mo of age)...
October 25, 2017: American Journal of Clinical Nutrition
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