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Iron homeostasis

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https://www.readbyqxmd.com/read/28335084/identification-of-new-bmp6-pro-peptide-mutations-in-patients-with-iron-overload
#1
Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least 5 different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28334935/genome-wide-association-study-of-iron-traits-and-relation-to-diabetes-in-the-hispanic-community-health-study-study-of-latinos-hchs-sol-potential-genomic-intersection-of-iron-and-glucose-regulation
#2
Laura M Raffield, Tin Louie, Tamar Sofer, Deepti Jain, Eli Ipp, Kent D Taylor, George J Papanicolaou, Larissa Avilés-Santa, Leslie A Lange, Cathy C Laurie, Matthew P Conomos, Timothy A Thornton, Yii-Der Ida Chen, Qibin Qi, Scott Cotler, Bharat Thyagarajan, Neil Schneiderman, Jerome I Rotter, Alex P Reiner, Henry J Lin
Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study (GWAS) of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; >12,000 participants) and also assessed the generalization of previously known loci to this population...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331855/diabetes-in-hfe-hemochromatosis
#3
REVIEW
James C Barton, Ronald T Acton
Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28330870/nuclear-factor-erythroid-2-related-factor-2-enhances-carcinogenesis-by-suppressing-apoptosis-and-promoting-autophagy-in-nickel-transformed-cells
#4
Young-Ok Son, Poyil Pratheeshkumar, Sasidharan Padmaja Divya, Zhuo Zhang, Xianglin Shi
Nickel-containing compounds are used widely in industry. Nickel is a known human carcinogen that primarily targets the lungs. Proposed mechanisms of nickel-induced carcinogenesis include disruption of cellular iron homeostasis, generation of reactive oxygen species (ROS), and induction of hypoxia signaling. The precise molecular mechanisms of nickel-induced malignant transformation and tumor development remain unclear. This study shows that the transcription factor Nrf2 is highly expressed in lung tumor tissue and in nickel-transformed human lung bronchial epithelial BEAS-2B cells (NiT cells)...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28328097/markers-of-iron-status-in-chronic-kidney-disease
#5
Adam E Gaweda
Anemia is one of the main comorbidities related to chronic kidney disease (CKD). Until the advent of erythropoiesis stimulating agents (ESA), endogenous erythropoietin deficiency has been thought to be the main culprit of anemia in CKD patients. The use of ESAs has shed new light on the physiology of CKD anemia, where iron homeostasis plays an increasingly important role. Disorders of iron homeostasis occurring in CKD turn the anemia management in those patients into a complex multifactorial therapeutic task, where ESA and Iron dose must be properly balanced to achieve the desired outcome without exposing the patients to the risk of serious adverse events...
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
#6
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/28324492/detection-of-hypoxia-induced-and-iron-depletion-induced-mitophagy-in-mammalian-cells
#7
Shun-Ichi Yamashita, Tomotake Kanki
Mitochondrial quality and quantity are not only regulated by mitochondrial fusion and fission but also by mitochondria degradation. Mitophagy, an autophagy specific for damaged or unnecessary mitochondria, is believed to be an important pathway for mitochondrial homeostasis. To date, several stimuli are known to induce mitophagy. Some of these stimuli, however, including hypoxia, iron depletion, and nitrogen starvation, induce mild mitophagy, which is difficult to detect through decreased mitochondrial mass...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28318006/inhibiting-the-bfrb-bfd-interaction-in-pseudomonas-aeruginosa-causes-irreversible-iron-accumulation-in-bacterioferritin-and-iron-deficiency-in-the-bacterial-cytosol
#8
Kate Eshelman, Huili Yao, Achala N D Punchi Hewage, Jacqueline J Deay, Josephine R Chandler, Mario Rivera
Iron is an essential nutrient for bacteria but the reactivity of Fe(2+) and the insolubility of Fe(3+) present significant challenges to bacterial cells. Iron storage proteins contribute to ameliorating these challenges by oxidizing Fe(2+) using O2 and H2O2 as electron acceptors, and by compartmentalizing Fe(3+). Two types of iron-storage proteins coexist in bacteria, the ferritins (Ftn) and the heme-containing bacterioferritins (Bfr), but the reasons for their coexistence are largely unknown. P. aeruginosa cells harbor two iron storage proteins (FtnA and BfrB), but nothing is known about their relative contributions to iron homeostasis...
March 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28316240/heme-gazing-illuminating-eukaryotic-heme-trafficking-dynamics-and-signaling-with-fluorescent-heme-sensors
#9
David A Hanna, Osiris Martinez-Guzman, Amit Ram Reddi
Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme dependent processes require the dynamic and rapid mobilization of heme from sites of synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitates that heme mobilization is carefully controlled to mitigate the deleterious effects of this essential toxin. Indeed, a number of disorders, including certain cancers, cardiovascular diseases, and aging and age-related neurodegenerative diseases, are tied to defects in heme homeostasis...
March 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28315258/mechanisms-of-iron-sensing-and-regulation-in-the-yeast-saccharomyces-cerevisiae
#10
REVIEW
María Teresa Martínez-Pastor, Ana Perea-García, Sergi Puig
Iron is a redox active element that functions as an essential cofactor in multiple metabolic pathways, including respiration, DNA synthesis and translation. While indispensable for eukaryotic life, excess iron can lead to oxidative damage of macromolecules. Therefore, living organisms have developed sophisticated strategies to optimally regulate iron acquisition, storage and utilization in response to fluctuations in environmental iron bioavailability. In the yeast Saccharomyces cerevisiae, transcription factors Aft1/Aft2 and Yap5 regulate iron metabolism in response to low and high iron levels, respectively...
April 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28304072/dealing-with-iron-metabolism-in-rice-from-breeding-for-stress-tolerance-to-biofortification
#11
Railson Schreinert Dos Santos, Artur Teixeira de Araujo, Camila Pegoraro, Antonio Costa de Oliveira
Iron is a well-known metal. Used by humankind since ancient times in many different ways, this element is present in all living organisms, where, unfortunately, it represents a two-way problem. Being an essential block in the composition of different proteins and metabolic pathways, iron is a vital component for animals and plants. That is why iron deficiency has a severe impact on the lives of different organisms, including humans, becoming a major concern, especially in developing countries where access to adequate nutrition is still difficult...
March 16, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28303424/inherited-disorders-of-transition-metal-metabolism-an-update
#12
REVIEW
Peter T Clayton
Elements with a biological role include six trace transition metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry...
March 16, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28303071/the-regulation-of-iron-absorption-and-homeostasis
#13
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
#14
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/28301981/alterations-of-hepatocyte-function-with-free-radical-generators-and-reparation-or-prevention-with-coffee-polyphenols
#15
Amel Saidi Merzouk, Merzouk Hafida, Amel Medjdoub, Bouchra Loukidi, Sabri Cherrak, Sid Ahmed Merzouk, Mourad Elhabiri
Liver diseases are linked in the majority of cases to oxidative stress that antioxidants could neutralize with reducing liver injury. Chlorogenic acid, a coffee polyphenol, possesses antioxidant prosperities. The aim of this study was to evaluate in vitro preventive and corrective effects of cholorogenic acid in hepatocyte toxicity induced by free radicals. Hepatocytes were isolated from adult male Wistar rats. To determine corrective effects and reparation, cells were first exposed to two free radical generators (Hydrogen peroxide/Iron sulfate for hydroxyl radical formation, and Phenazine methosulfate/Nicotinamide adenine dinucleotide for superoxide anion formation) for 12H and thereafter treated by chlorogenic acid (1 and 10 µM final concentration) for another 12H...
March 16, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28296010/overview-of-iron-metabolism-in-health-and-disease
#16
Som Dev, Jodie L Babitt
Iron is an essential element for numerous fundamental biologic processes, but excess iron is toxic. Abnormalities in systemic iron balance are common in patients with chronic kidney disease and iron administration is a mainstay of anemia management in many patients. This review provides an overview of the essential role of iron in biology, the regulation of systemic and cellular iron homeostasis, how imbalances in iron homeostasis contribute to disease, and the implications for chronic kidney disease patients...
March 15, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28295188/how-we-manage-iron-overload-in-sickle-cell-patients
#17
REVIEW
Thomas D Coates, John C Wood
Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28289146/the-pseudomonas-aeruginosa-prrf-small-rnas-regulate-iron-homeostasis-during-acute-murine-lung-infection
#18
Alexandria A Reinhart, Angela T Nguyen, Luke K Brewer, Justin Bevere, Jace W Jones, Maureen A Kane, F Heath Damron, Mariette Barbier, Amanda G Oglesby-Sherrouse
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs, which block the expression of iron-containing proteins in iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal, a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the prrF genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the prrF1-prrF2 intergenic sequence (the PrrH-IG sequence)...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28287621/restoring-the-impaired-cardiac-calcium-homeostasis-and-cardiac-function-in-iron-overload-rats-by-the-combined-deferiprone-and-n-acetyl-cysteine
#19
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Siriporn C Chattipakorn, Nipon Chattipakorn
Intracellular calcium [Ca(2+)]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287409/sirtuin-2-regulates-cellular-iron-homeostasis-via-deacetylation-of-transcription-factor-nrf2
#20
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...
March 13, 2017: Journal of Clinical Investigation
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