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Iron AND Transferrin

Anas Shamsi, Moyad Al Shahwan, Shahzaib Ahamad, Md Imtaiyaz Hassan, Faizan Ahmad, Asimul Islam
Donepezil, a highly selective and reversible inhibitor, is amongst the widely used drugs for treatment of Alzheimer's disease (AD) across the globe. Clinically significant human transferrin (hTf) is a key player involved in iron metabolism. The current study targets to have an insight into the interaction between donepezil and this plasma protein, hTf using UV-vis absorbance, fluorescence, isothermal titration calorimetry, circular dichroism and molecular docking techniques. UV spectroscopy of hTf in the presence of donepezil revealed the occurrence of hyperchromism coupled with blue shift in indicating complex formation...
March 21, 2019: Journal of Biomolecular Structure & Dynamics
Himanshu Malhotra, Manoj Kumar, Anoop Singh Chauhan, Asmita Dhiman, Surbhi Chaudhary, Anil Patidar, Pallavi Jaiswal, Kapil Sharma, Navdeep Sheokand, Chaaya Iyengar Raje, Manoj Raje
BACKGROUND/AIMS: Hypoxia triggers a rapid increase in iron demand to meet the requirements of enhanced erythropoiesis. The mobilization of iron stores from macrophage to plasma as holo-transferrin (Tf) from where it is accessible to erythroid precursor cells impacts iron homeostasis. Despite the immediate need for enhanced iron uptake by bone marrow cells, numerous studies have shown that transferrin receptor levels do not rise until more than 24 hours after the onset of hypoxia, suggesting the existence of heretofore unknown rapid response cellular machinery for iron acquisition in the early stages of cellular hypoxia...
2019: Cellular Physiology and Biochemistry
Vadim B Vasilyev
Ceruloplasmin (CP) is a mammalian blood plasma ferroxidase. More than 95% of the copper found in plasma is carried by this protein, which is a member of the multicopper oxidase family. Proteins from this group are able to oxidize substrates through the transfer of four electrons to oxygen. The essential role of CP in iron metabolism in humans is particularly evident in the case of loss-of-function mutations in the CP gene resulting in a neurodegenerative syndrome known as aceruloplasminaemia. However, the functions of CP are not limited to the oxidation of ferrous iron to ferric iron, which allows loading of the ferric iron into transferrin and prevents the deleterious reactions of Fenton chemistry...
March 20, 2019: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Sahil Chawla, Seema Gulyani, Richard P Allen, Christopher J Earley, Xu Li, Peter Van Zijl, Dimitrios Kapogiannis
Study ObjectivesDetermine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in Restless Legs Syndrome (RLS). METHODS: We used immunoprecipitation for neuronal marker L1CAM to isolate nEVs from the serum of 20 RLS subjects from a study including MRI determinations of iron deposition in the substantia nigra and hematologic parameters and 28 age- and sex-matched Controls. RESULTS: RLS compared to Control subjects showed higher levels of nEV total ferritin but similar levels of transferrin receptor and ferroportin...
March 21, 2019: Sleep
Simona Hildegard Stancu, Ana Stanciu, Mariana Lipan, Cristina Capusa
Rationale: Anemia, a common feature in chronic kidney disease (CKD), has multiple contributors to its pathogenesis. Besides the well recognized erythropoietin and iron deficiencies, hydration status might be involved. Objective: To assess the prevalence and correlations of anemia, iron deficiency and overhydration in patients with stage 2 to 5 CKD. Methods and Results: This cross-sectional study enrolled 125 erythropoietin and iron therapy naïve non-dialysis CKD patients, without a identifiable cause of anemia...
October 2018: Journal of Medicine and Life
Sun Hwa Lee, Eun Jin Yang
Neuroinflammation is considered a critical factor in the pathologic mechanisms of amyotrophic lateral sclerosis (ALS). This study examined the levels of neuroinflammatory proteins in the spinal cord of JGT-treated hSOD1 G93A transgenic mice to determine the effect of Jaeumganghwa-Tang (JGT) on neuroinflammation. Twelve 8-week-old male experimental mice were randomly allocated to three groups: a non-transgenic group, a hSOD1G93A transgenic group, and a hSOD1G93A transgenic group that received JGT 1 mg/g orally once daily for 6 weeks...
2019: Evidence-based Complementary and Alternative Medicine: ECAM
Veronica Paterlini, Nadia Maria Porpiglia, Elio Franco De Palo, Franco Tagliaro
Asialo-human transferrin (asialo-hTf) is a glycoform of the human serum protein transferrin characterized by the lack of the sialic acid (SA) terminal unit. It is known that glycosylation micro-heterogeneity and the presence of SA are strongly involved in protein functioning and patho-physiological activities. Some hTf glycoforms are valuable biomarkers for the detection of both genetic defects of glycosylation and/or sialoform distribution changes. The determination of the carbohydrate deficient transferrin (CDT) glycoforms is currently a widely employed method for the diagnosis of chronic alcohol abuse...
March 16, 2019: Alcohol
Amy D Mackay, Erik D Marchant, Devin J Munk, Richard K Watt, Jason M Hansen, David M Thomson, Chad R Hancock
Doxorubicin (DOX) is an effective chemotherapeutic treatment with lasting side effects in heart and skeletal muscle. DOX is known to bind with iron, contributing to oxidative damage resulting in cardiac and skeletal muscle toxicity. However, major cellular changes to iron regulation in response to DOX are poorly understood in liver, heart and skeletal muscle. Additionally, two co-treatments, exercise (EX) or metformin (MET) were studied for their effectiveness in reducing DOX toxicity through ameliorating iron dysregulation and preventing oxidative stress...
March 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Martina Rauner, Ulrike Baschant, Antonella Roetto, Rosa Maria Pellegrino, Sandra Rother, Juliane Salbach-Hirsch, Heike Weidner, Vera Hintze, Graeme Campbell, Andreas Petzold, Regis Lemaitre, Ian Henry, Teresita Bellido, Igor Theurl, Sandro Altamura, Silvia Colucci, Martina U Muckenthaler, Georg Schett, Davide Komla Ebri, J H Duncan Bassett, Graham R Williams, Uwe Platzbecker, Lorenz C Hofbauer
Transferrin receptor 2 (Tfr2) is mainly expressed in the liver and controls iron homeostasis. Here, we identify Tfr2 as a regulator of bone homeostasis that inhibits bone formation. Mice lacking Tfr2 display increased bone mass and mineralization independent of iron homeostasis and hepatic Tfr2. Bone marrow transplantation experiments and studies of cell-specific Tfr2 knockout mice demonstrate that Tfr2 impairs BMP-p38MAPK signaling and decreases expression of the Wnt inhibitor sclerostin specifically in osteoblasts...
January 2019: Nature metabolism
Balaji Srinivasan, Julia L Finkelstein, Dakota O'Dell, David Erickson, Saurabh Mehta
BACKGROUND: Iron deficiency (ID) and anaemia are major health concerns, particularly in young children. Screening for ID based on haemoglobin (Hb) concentration alone has been shown to lack sensitivity and specificity. The American Academy of Pediatrics (AAP) recommends soluble transferrin receptor (sTfR) as a promising approach to screen for iron deficiency. However, in most settings, assessment of iron status requires access to centralized laboratories. There is an urgent need for rapid, sensitive, and affordable diagnostics for sTfR at the point-of-care...
March 15, 2019: EBioMedicine
Lokpati Mishra, Sawant Pramilla Damodar, Mahesh Sundararajan, Tusar Bandyopadhyay
Human serum transferrin (sTf) can also function as a noniron metal transporter, since only 30% of it is typically saturated with ferric ion. While this function of sTf can be fruitfully utilized for targeted delivery of certain metal therapeutics, it also runs the risk of trafficking the lethal radionuclides into cells. A large number of actinide (An) ions are known to bind to the iron sites of sTf, although molecular level understanding of their binding is unclear. Understanding the radionuclide interaction with sTf is a primary step towards future design of their decorporating agents, since irrespective of the means of contamination, the radionuclides are absorbed and transported by blood before depositing into target organs...
March 13, 2019: Journal of Physical Chemistry. B
Nicola M Martin, Cathryn A Conlon, Rebecca J M Smeele, Owen A R Mugridge, Pamela R von Hurst, James P McClung, Kathryn L Beck
Decreases in Fe status have been reported in military women during initial training periods of 8-10 weeks. The present study aimed to characterise Fe status and associations with physical performance in female New Zealand Army recruits during a 16-week basic combat training (BCT) course. Fe status indicators - Hb, serum ferritin (sFer), soluble transferrin receptor (sTfR), transferrin saturation (TS) and erythrocyte distribution width (RDW) - were assessed at the beginning (baseline) and end of BCT in seventy-six volunteers without Fe-deficiency non-anaemia (sFer 10 mg/l at baseline or end...
March 13, 2019: British Journal of Nutrition
Cristina Barale, Rouslan Senkeev, Franca Napoli, Marco De Gobbi, Angelo Guerrasio, Alessandro Morotti, Isabella Russo
BACKGROUND:  The association between iron overload (IO) and risk of cardiovascular disease is controversial. Epidemiological studies have found a significant negative association of transferrin (Tf) saturation and cardiovascular events suggesting that higher body iron possibly confer a protective effect towards developing cardiovascular events. The biological mechanisms of this phenomenon are unknown. OBJECTIVE:  This article investigates the role of IO on platelet reactivity...
March 12, 2019: Thrombosis and Haemostasis
Marine Hubert, Baptiste Gaudriot, Sebastien Biedermann, Hervé Gouezec, Emmanuelle Sylvestre, Guillaume Bouzille, Jean-Philippe Verhoye, Erwan Flecher, Claude Ecoffey
OBJECTIVE: To evaluate the incidence and consequences of preoperative iron deficiency in elective cardiac surgery. DESIGN: A prospective observational study. SETTING: The cardiac surgery unit of a university hospital, from November 2016 to February 2017. PARTICIPANTS: All patients presenting for elective cardiac surgery during the study period, with the exclusion of noncardiac thoracic surgeries, surgeries of the descending aorta, endovascular procedures, and patients affected by an iron-metabolism disease...
February 11, 2019: Journal of Cardiothoracic and Vascular Anesthesia
Alejandra María Gómez-Gutiérrez, Beatriz Elena Parra-Sosa, Julio Cesar Bueno-Sánchez
Objective: To examine the expression of hypoxia-inducible factor-1 α (HIF-1 α ), TfR1, and TfR1-attached terminal monosaccharides in placentas of women with IDAP and severe preeclampsia. Methods: TfR1 and HIF-1 α were detected by western blot. Immunoadsorption of TfR1 was performed to characterize the terminal monosaccharides by specific lectin binding. Results: There was no difference in the expression of TfR1 and HIF-1 α between groups...
2019: Journal of Pregnancy
Yunhe Lang, Lei Shi, Ling Lan, Zheng Zhao, Dawei Yang, Yao Fu, Yalin Tang, Xiufeng Zhang
In this work, a new biological probe for human transferrin (hTf) detection based on a cyanine dye ETC supramolecular assembly was designed. In sub-micromolar level, apo-hTf could induced the ETC aggregations transferred from H-aggregations to J-band with color change from pink to blue, while holo-hTf hardly possessed the ability, indicating ETC could specifically identify apo-hTf. The present study allowed for apo-hTf detection in the range of 8-80 nM with a detection limit of 2.8 nM and the sensitivity of visualization was around 70 nM...
February 21, 2019: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Linda Celeste Montemiglio, Claudia Testi, Pierpaolo Ceci, Elisabetta Falvo, Martina Pitea, Carmelinda Savino, Alessandro Arcovito, Giovanna Peruzzi, Paola Baiocco, Filippo Mancia, Alberto Boffi, Amédée des Georges, Beatrice Vallone
Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded transferrin and ferritin. Arenaviruses and the malaria parasite exploit CD71 for cell invasion and epitopes on CD71 for interaction with transferrin and pathogenic hosts were identified. Here, we provide the molecular basis of the CD71 ectodomain-human ferritin interaction by determining the 3.9 Å resolution single-particle cryo-electron microscopy structure of their complex and by validating our structural findings in a cellular context...
March 8, 2019: Nature Communications
Hadar Moran-Lev, Tut Galai, Anat Yerushalmy-Feler, Yosef Weisman, Adi Anafi, Varda Deutsch, Michal Cipok, Ronit Lubetzky, Shlomi Cohen
BACKGROUND AND AIMS: The role of hepcidin in inflammatory bowel disease (IBD) children with anemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD pediatric patients. METHODS: Eighty-five children were prospectively recruited in the Dana-Dwek Children's Hospital (40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13...
March 6, 2019: Journal of Crohn's & Colitis
Matthias Diebold, Andreas D Kistler
BACKGROUND: Iron is administered intravenously (IV) to many dialysis patients at regular intervals and iron stores are evaluated through periodic measurements of ferritin and transferrin saturation (TSAT). In patients without kidney diseases, large single doses of IV iron lead to a transient rise in serum ferritin that does not reflect iron stores. It is not known whether and to what extent smaller IV iron doses used to maintain adequate stores in hemodialysis patients lead to transient spurious elevations of ferritin and TSAT...
March 1, 2019: BMC Nephrology
Cristian Fava, Massimo Piepoli, Giovanni Q Villani
Heart failure with reduced ejection fraction (HFrEF) is a clinical reality with an incidence of >10% in the population over 65 years of age, expected to increase in the coming years. Alongside the well-known pharmacological options (e.g. angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, neprilysin inhibitors, beta-blockers, aldosterone antagonists), which have significantly improved the clinical and prognostic outcomes of HFrEF patients, we now have a new therapeutic target: iron deficiency, defined as a ferritin concentration <100 μg/l or between 100-300 μg/l in the presence of a transferrin saturation <20%...
March 2019: Giornale Italiano di Cardiologia
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