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https://www.readbyqxmd.com/read/28426710/change-in-iron-metabolism-in-rats-after-renal-ischemia-reperfusion-injury
#1
Guang-Liang Xie, Lin Zhu, Yan-Min Zhang, Qian-Nan Zhang, Qing Yu
Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1) and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI). In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI...
2017: PloS One
https://www.readbyqxmd.com/read/28414228/molecular-aspects-of-a-robust-assay-for-ferroxidase-function-of-ceruloplasmin
#2
Laura Cortes, Blaine R Roberts, Anthony G Wedd, Zhiguang Xiao
Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and plays an essential role in the metabolism of iron in mammals. Ferrous ion supplied by the ferroportin exporter is converted by Cp to ferric ion that is accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the atomic and molecular level has been hampered by the lack of a suitable ferrous substrate. We have developed the classic chromophoric complex Fe(II)Hx(Tar)2 (H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a robust substrate for evaluation of the ferroxidase function of Cp and related enzymes...
April 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28361857/artemisinin-modulating-effect-on-human-breast-cancer-cell-lines-with-different-sensitivity-to-cytostatics
#3
V F Chekhun, N Yu Lukianova, T V Borikun, T V Zadvorny, A Mokhir
AIM: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin - Dox; cisplatin - DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. MATERIALS AND METHODS: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28338217/fasting-up-regulates-ferroportin-1-expression-via-a-ghrelin-ghsr-mapk-signaling-pathway
#4
Qian-Qian Lou, Yu-Fu Zhou, Mesona Yung-Jin Chen, Li Liu, Juan Ma, Meng-Wan Zhang, Fa-Li Zhang, Ya Ke, Zhong-Ming Qian
The significant positive correlation between ghrelin and iron and hepcidin levels in the plasma of children with iron deficiency anemia prompted us to hypothesize that ghrelin may affect iron metabolism. Here, we investigated the effects of fasting or ghrelin on the expression of hepcidin, ferroportin 1 (Fpn1), transferrin receptor 1 (TfR1), ferritin light chain (Ft-L) proteins and ghrelin, and also hormone secretagogue receptor 1 alpha (GHSR1α) and ghrelin O-acyltransferase (GOAT) mRNAs in the spleen and/or macrophage...
March 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28335378/bioavailability-of-microencapsulated-iron-from-fortified-bread-assessed-using-piglet-model
#5
Malgorzata A Bryszewska, Luca Laghi, Augusta Zannoni, Andrea Gianotti, Francesca Barone, Danielle L Taneyo Saa, Maria L Bacci, Domenico Ventrella, Monica Forni
The aim of this study was to investigate the influence of oral iron supplementation, in the form of fortified breads, on the growth performance, health, iron status parameters, and fecal metabolome of anemic piglets. A study was conducted on 24 hybrid (Large White × Landrace × Duroc) piglets. From day 44, the post-natal 12 piglets were supplemented with 100 g of one of two experimental breads, each fortified with 21 mg of ferrous sulphate, either encapsulated or not. After one week of oral supplementation, hematological parameters (hematocrit value, hemoglobin, and red blood cells) showed statistically significant differences (p ≤ 0...
March 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28328181/role-of-hepcidin-ferroportin-axis-in-the-pathophysiology-diagnosis-and-treatment-in-anemia-of-chronic-inflammation
#6
Arielle L Langer, Yelena Z Ginzburg
Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis...
March 22, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28327200/a-first-in-human-phase-1-study-of-a-hepcidin-monoclonal-antibody-ly2787106-in-cancer-associated-anemia
#7
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W Goldman, David A Smith, Christopher A Slapak, Robert L Ilaria, Ramon V Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L Tuttle, Yiu-Keung Lau, Eric J Roeland
BACKGROUND: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28319068/iron-addiction-a-novel-therapeutic-target-in-ovarian-cancer
#8
D Basuli, L Tesfay, Z Deng, B Paul, Y Yamamoto, G Ning, W Xian, F McKeon, M Lynch, C P Crum, P Hegde, M Brewer, X Wang, L D Miller, N Dyment, F M Torti, S V Torti
Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs)...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28303071/the-regulation-of-iron-absorption-and-homeostasis
#9
REVIEW
Daniel F Wallace
Iron is an essential element in biology, required for numerous cellular processes. Either too much or too little iron can be detrimental, and organisms have developed mechanisms for balancing iron within safe limits. In mammals there are no controlled mechanisms for the excretion of excess iron, hence body iron homeostasis is regulated at the sites of absorption, utilisation and recycling. This review will discuss the discoveries that have been made in the past 20 years into advancing our understanding of iron homeostasis and its regulation...
May 2016: Clinical Biochemist. Reviews
https://www.readbyqxmd.com/read/28302014/role-of-hepcidin-25-in-chronic-kidney-disease-anemia-and-beyond
#10
Norishi Ueda, Kazuya Takasawa
Iron is an essential element for all living organisms, but produces toxic oxidants. Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin, inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron status and the response to iron supplementation or erythropoietin-stimulating agents...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28287409/sirtuin-2-regulates-cellular-iron-homeostasis-via-deacetylation-of-transcription-factor-nrf2
#11
Xiaoyan Yang, Seong-Hoon Park, Hsiang-Chun Chang, Jason S Shapiro, Athanassios Vassilopoulos, Konrad T Sawicki, Chunlei Chen, Meng Shang, Paul W Burridge, Conrad L Epting, Lisa D Wilsbacher, Supak Jenkitkasemwong, Mitchell Knutson, David Gius, Hossein Ardehali
SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron levels both in vitro and in vivo. Mechanistically, we determined that SIRT2 maintains cellular iron levels by binding to and deacetylating nuclear factor erythroid-derived 2-related factor 2 (NRF2) on lysines 506 and 508, leading to a reduction in total and nuclear NRF2 levels...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28286378/iron-reduces-m1-macrophage-polarization-in-raw264-7-macrophages-associated-with-inhibition-of-stat1
#12
Zhen-Shun Gan, Qian-Qian Wang, Jia-Hui Li, Xu-Liang Wang, Yi-Zhen Wang, Hua-Hua Du
Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28273797/partially%C3%A2-hydrolyzed%C3%A2-guar%C3%A2-gum%C3%A2-increases%C3%A2-ferroportin%C3%A2-expression%C3%A2-in%C3%A2-the%C3%A2-colon%C3%A2-of%C3%A2-anemic%C3%A2-growing%C3%A2-rats
#13
Luciana Carvalho, Débora Brait, Márcia Vaz, Pablo Lollo, Priscila Morato, Silvia Oesterreich, Jorge Raposo, Karine Freitas
Studies have reported a positive effect of prebiotics on the bioavailability of iron. This study evaluated the effect of partially hydrolyzed guar gum (PHGG) on iron absorption mechanisms in anemic rats. Male Wistar rats were fed 75g American Institute of Nutrition Rodent Diets for growth, pregnancy and lactation (AIN93-G) without iron for three weeks in order to induce iron deficiency anemia. Then they were fed a control diet (n = 12; without fiber) or a diet with 7.5% of PHGG (n = 12), both without iron. Food intake, body growth and the feed efficiency coefficient (FEC) were measured...
March 3, 2017: Nutrients
https://www.readbyqxmd.com/read/28228829/hepatic-iron-storage-is-related-to-body-adiposity-and-hepatic-inflammation
#14
Chan Yoon Park, Jayong Chung, Kyung-Ok Koo, Min Soo Kim, Sung Nim Han
BACKGROUND: Obesity has been reported to be associated with iron deficiency. However, few studies have investigated iron status in low adiposity. To investigate whether body adiposity was associated with altered hepatic iron status, we compared liver iron levels and markers involved in inflammation and iron absorption in obese, control, and mildly calorie restricted mice. METHODS: Seven week old C57BL/6 mice were fed control (10% kcal fat, Control) or high fat (60% kcal fat, HFD) diets, or reduced amount of control diet to achieve 15% calorie restriction (CR) for 16 weeks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28219768/copper-therapy-reduces-intravascular-hemolysis-and-derepresses-ferroportin-in-mice-with-mosaic-mutation-atp7a-mo-ms-an-implication-for-copper-mediated-regulation-of-the-slc40a1-gene-expression
#15
Małgorzata Lenartowicz, Rafał R Starzyński, Aneta Jończy, Robert Staroń, Justyna Antoniuk, Wojciech Krzeptowski, Paweł Grzmil, Aleksandra Bednarz, Olga Pierzchała, Mateusz Ogórek, Zenon Rajfur, Zbigniew Baster, Paweł Lipiński
Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28216608/expression-of-iron-related-proteins-differentiate-non-cancerous-and-cancerous-breast-tumors
#16
Sara Pizzamiglio, Maida De Bortoli, Elena Taverna, Michele Signore, Silvia Veneroni, William Chi-Shing Cho, Rosaria Orlandi, Paolo Verderio, Italia Bongarzone
We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA) or reverse-phase protein array (RPPA), were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28203649/increased-iron-export-by-ferroportin-induces-restriction-of-hiv-1-infection-in-sickle-cell-disease
#17
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Advances
https://www.readbyqxmd.com/read/28188131/momelotinib-inhibits-acvr1-alk2-decreases-hepcidin-production-and-ameliorates-anemia-of-chronic-disease-in-rodents
#18
Malte Asshoff, Verena Petzer, Matthew R Warr, David Haschka, Piotr Tymoszuk, Egon Demetz, Markus Seifert, Wilfried Posch, Manfred Nairz, Pat Maciejewski, Peter Fowles, Christopher J Burns, Gregg Smith, Kay-Uwe Wagner, Guenter Weiss, J Andrew Whitney, Igor Theurl
Patients with myelofibrosis (MF) often develop anemia and frequently become dependent on red blood cell transfusions. Results from a phase 2 study for the treatment of MF with the Janus kinase1/2 (JAK1/2) inhibitor momelotinib (MMB) demonstrated that MMB treatment ameliorated anemia, unexpected for a JAK1/2 inhibitor, as erythropoietin-mediated JAK2 signaling is essential for erythropoiesis. Using a rat model of anemia of chronic disease (ACD), we now demonstrate that MMB treatment can normalize hemoglobin and red blood cell numbers...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28159226/the-effect-of-amino-acid-deprivation-on-the-transfer-of-iron-through-caco-2-cell-monolayers
#19
Guenievre Roussel, Valerie Stevens, Sarah Cottin, Harry J McArdle
Iron (Fe) metabolism is modified by many nutritional factors. Amino acids (AA) play a central role in various biological processes, such as protein synthesis and energy supply. However, the influence of AA status on iron metabolism has not been investigated. Here, we test whether AA alters iron metabolism in an intestinal cell model. Both Fe uptake and transfer across the cell monolayer were significantly increased by non-essential AA deficiency (both p<0.001) while only Fe transfer was increased by essential AA deficiency (p<0...
March 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28143953/hemolytic-anemia-repressed-hepcidin-level-without-hepatocyte-iron-overload-lesson-from-g%C3%A3-nther-disease-model
#20
Sarah Millot, Constance Delaby, Boualem Moulouel, Thibaud Lefebvre, Nathalie Pilard, Nicolas Ducrot, Cécile Ged, Philippe Lettéron, Lucia de Franceschi, Jean Charles Deybach, Carole Beaumont, Laurent Gouya, Hubert De Verneuil, Saïd Lyoumi, Hervé Puy, Zoubida Karim
Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1...
February 2017: Haematologica
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