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Iron homeostasis

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https://www.readbyqxmd.com/read/29227619/small-molecule-chelators-reveal-that-iron-starvation-inhibits-late-stages-of-bacterial-cytokinesis
#1
Thiago M A Santos, Matthew G Lammers, Maoquan Zhou, Ian L Sparks, Madhusudan Rajendran, Dong Fang, Crystal L Y De Jesus, Gabriel F R Carneiro, Qiang Cui, Douglas B Weibel
Bacterial cell division requires identification of the division site, assembly of the division machinery, and constriction of the cell envelope. These processes are regulated in response to several cellular and environmental signals. Here, we use small molecule iron chelators to characterize the surprising connections between bacterial iron homeostasis and cell division. We demonstrate that iron starvation downregulates the transcription of genes encoding proteins involved in cell division, reduces protein biosynthesis, and prevents correct positioning of the division machinery at the division site...
December 11, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29227325/study-of-insulin-resistance-in-patients-with-%C3%AE-thalassemia-major-and-validity-of-triglyceride-glucose-tyg-index
#2
Arif M Ansari, Kamalakshi G Bhat, Smitha S Dsa, Soundarya Mahalingam, Nitin Joseph
Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied...
December 8, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29225034/cytosolic-iron-sulfur-assembly-is-evolutionarily-tuned-by-a-cancer-amplified-ubiquitin-ligase
#3
Jenny L Weon, Seung Wook Yang, Patrick Ryan Potts
The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway functions to incorporate inorganic Fe-S cofactors into a variety of proteins, including several DNA repair enzymes. However, the mechanisms regulating the CIA pathway are unknown. We describe here that the MAGE-F1-NSE1 E3 ubiquitin ligase regulates the CIA pathway through ubiquitination and degradation of the CIA-targeting protein MMS19. Overexpression or knockout of MAGE-F1 altered Fe-S incorporation into MMS19-dependent DNA repair enzymes, DNA repair capacity, sensitivity to DNA-damaging agents, and iron homeostasis...
November 30, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29224080/anemia-and-iron-status-among-different-body-size-phenotypes-in-chinese-adult-population-a-nation-wide-health-and-nutrition-survey
#4
Jiang Li, Cheng Xiao, Hui Yang, Yun Zhou, Rui Wang, Yongtong Cao
Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes...
December 9, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29222343/bacterial-cyclic-%C3%AE-1-2-glucans-sequester-iron-to-protect-against-iron-induced-toxicity
#5
Sreegowrinadh Javvadi, Sheo Shankar Pandey, Amita Mishra, Binod Bihari Pradhan, Subhadeep Chatterjee
Cellular iron homeostasis is critical for survival and growth. Bacteria employ a variety of strategies to sequester iron from the environment and to store intracellular iron surplus that can be utilized in iron-restricted conditions while also limiting the potential for the production of iron-induced reactive oxygen species (ROS). Here, we report that membrane-derived oligosaccharide (mdo) glucan, an intrinsic component of Gram-negative bacteria, sequesters the ferrous form of iron. Iron-binding, uptake, and localization experiments indicated that both secreted and periplasmic β-(1,2)-glucans bind iron specifically and promote growth under iron-restricted conditions...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29213059/a-comprehensive-assessment-of-the-genetic-determinants-in-salmonella-typhimurium-for-resistance-to-hydrogen-peroxide-using-proteogenomics
#6
Sardar Karash, Rohana Liyanage, Abdullah Qassab, Jackson O Lay, Young Min Kwon
Salmonella is an intracellular pathogen infecting a wide range of hosts and can survive in macrophages. An essential mechanism used by macrophages to eradicate Salmonella is production of reactive oxygen species. Here, we used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a saturated Tn5 insertion library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes required for resistance of S...
December 6, 2017: Scientific Reports
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
#7
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/29210994/iron-supplementation-during-pregnancy-and-infancy-uncertainties-and-implications-for-research-and-policy
#8
REVIEW
Patsy M Brannon, Christine L Taylor
Iron is particularly important in pregnancy and infancy to meet the high demands for hematopoiesis, growth and development. Much attention has been given to conditions of iron deficiency (ID) and iron deficient anemia (IDA) because of the high global prevalence estimated in these vulnerable life stages. Emerging and preliminary evidence demonstrates, however, a U-shaped risk at both low and high iron status for birth and infant adverse health outcomes including growth, preterm birth, gestational diabetes, gastrointestinal health, and neurodegenerative diseases during aging...
December 6, 2017: Nutrients
https://www.readbyqxmd.com/read/29209212/identification-of-antibody-and-small-molecule-antagonists-of-ferroportin-hepcidin-interaction
#9
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/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#10
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...
December 5, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29208364/dopamine-promotes-cellular-iron-accumulation-and-oxidative-stress-responses-in-macrophages
#11
Stefanie Dichtl, David Haschka, Manfred Nairz, Markus Seifert, Chiara Volani, Oliver Lutz, Günter Weiss
Iron is essential for many biological functions including neurotransmitter synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts tyrosine to dopamine and further to norepinephrine. As the shared chemical structure, called catechol, may potentially bind iron we questioned whether tyrosine derived hormones would impact on cellular iron homeostasis in macrophages, which are central for the maintenance of body iron homeostasis. Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect of catecholamines and found that only dopamine but neither tyrosine, nor norepinephrine, affected cellular iron homeostasis...
December 2, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29206303/the-iron-regulated-transporter-1-plays-an-essential-role-in-uptake-translocation-and-grain-loading-of-manganese-but-not-iron-in-barley
#12
Lizhi Long, Daniel P Persson, Fengying Duan, Kirsten Jørgensen, Lixing Yuan, Jan K Schjoerring, Pai R Pedas
Transporters involved in manganese (Mn) uptake and intracellular Mn homeostasis in Arabidopsis and rice are well characterized, while much less is known for barley, which is particularly prone to Mn deficiency. In this study we have investigated the role of the iron-regulated transporter 1 (IRT1) for Mn uptake and translocation in barley plants. We employed an RNAi approach to reduce HvIRT1 expression to 5% of the wild-type level. This enabled characterization of the functional role of HvIRT1 by use of advanced imaging and phenotyping techniques applied to plants growing in hydroponics or soils with different Mn availability...
December 5, 2017: New Phytologist
https://www.readbyqxmd.com/read/29201641/iron-related-gene-variants-and-brain-iron-in-multiple-sclerosis-and-healthy-individuals
#13
Jesper Hagemeier, Murali Ramanathan, Ferdinand Schweser, Michael G Dwyer, Fuchun Lin, Niels Bergsland, Bianca Weinstock-Guttman, Robert Zivadinov
Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29196967/modern-iron-replacement-therapy-clinical-and-pathophysiological-insights
#14
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/29191734/splenomegaly-pathophysiological-bases-and-therapeutic-options
#15
Campbell V McKenzie, Chanukya K Colonne, Jia Hao Yeo, Stuart T Fraser
The spleen is the largest immune organ in the human body and is also essential for red blood cell homeostasis and iron recycling. An average human spleen is approximately 10 centimetres in length and weighs 150g. Pathological conditions can result in the spleen weighing in excess of 2000g and extending over 30 centrimetres in length. This remarkable property of the spleen to expand is termed splenomegaly. Splenomegaly can occur as a physiological response to stress or as a chronic process that is often detrimental to the wellbeing of the individual...
December 2, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29183916/ceruloplasmin-replacement-therapy-ameliorates-neurological-symptoms-in-a-preclinical-model-of%C3%A2-aceruloplasminemia
#16
Alan Zanardi, Antonio Conti, Marco Cremonesi, Patrizia D'Adamo, Enrica Gilberti, Pietro Apostoli, Carlo Vittorio Cannistraci, Alberto Piperno, Samuel David, Massimo Alessio
Aceruloplasminemia is a monogenic disease caused by mutations in the ceruloplasmin gene that result in loss of protein ferroxidase activity. Ceruloplasmin plays a role in iron homeostasis, and its activity impairment leads to iron accumulation in liver, pancreas, and brain. Iron deposition promotes diabetes, retinal degeneration, and progressive neurodegeneration. Current therapies mainly based on iron chelation, partially control systemic iron deposition but are ineffective on neurodegeneration. We investigated the potential of ceruloplasmin replacement therapy in reducing the neurological pathology in the ceruloplasmin-knockout (CpKO) mouse model of aceruloplasminemia...
November 28, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29182758/microrna-122-targets-genes-related-to-goose-fatty-liver
#17
Jun Zhang, Qian Wang, Xing Zhao, Laidi Wang, Xingguo Wang, Jian Wang, Biao Dong, Daoqing Gong
MicroRNA-122 (miR-122), a completely conserved, liver-specific miRNA in vertebrates, is essential for the maintenance of liver homeostasis. This 22-nucleotide-length RNA regulates diverse functions such as cholesterol, glucose, and lipid metabolism as well as iron homeostasis and infection of hepatitis C virus (HCV). Landes goose, which has a good, fatty liver, has important significance for us in studying miR-122 function in goose fatty liver. In the current study, we identified miR-122 in goose liver and its expression pattern and target genes...
November 22, 2017: Poultry Science
https://www.readbyqxmd.com/read/29180001/effect-of-the-fe2-chelation-by-2-2-dipyridyl-in-the-doxorubicin-induced-lethality-in-breast-tumor-cell-lines
#18
Jéssica R Bernardes, Caroline C de Faria, Iris S Andrade, Andrea Claudia Freitas Ferreira, Denise P Carvalho, Alvaro C Leitão, Tatiana A M de Alencar, Rodrigo S Fortunato
Breast cancer cells may exhibit changes in iron homeostasis, which results in increased labile iron pool (LIP) levels. Several studies highlight the crucial role of high LIP levels in the maintenance of tumor cell physiology. Iron chelators have been tested in anticancer therapy in combination with chemotherapeutic agents, to improve drug efficacy. Thus, the aim of this study was to evaluate the effect of 2,2'-dipyridyl (DIP), a Fe2+ chelator, in combination with doxorubicin (DOX) in breast tumor cells. The maximum concentration of DIP that did not significantly reduce the viability of MDA-MB-231 cells was 10μM and for MCF-7 cells was 50μM...
November 24, 2017: Life Sciences
https://www.readbyqxmd.com/read/29179120/metal-homeostasis-in-the-pathobiology-of-the-opportunistic-human-fungal-pathogen-aspergillus-fumigatus
#19
REVIEW
Michael Blatzer, Jean-Paul Latgé
In contrast to obligate pathogens opportunistic pathogens such as Aspergillus fumigatus do not need a specific host to propagate or survive. However several characteristics of the saprophytic life-style and the selective pressure encountered in the primary ecological niche contribute to the virulence of A. fumigatus. All fungi depend on metals for growth and proliferation, like iron, copper, zinc, manganese or calcium. In the recent past several studies explored the manifold impact of metals modulating virulence of pathogens...
November 24, 2017: Current Opinion in Microbiology
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
#20
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
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