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Iron homeostasis

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https://www.readbyqxmd.com/read/29453656/the-ferroportin-ceruloplasmin-system-and-the-mammalian-iron-homeostasis-machine-regulatory-pathways-and-the-role-of-lactoferrin
#1
Maria Carmela Bonaccorsi di Patti, Antimo Cutone, Fabio Polticelli, Luigi Rosa, Maria Stefania Lepanto, Piera Valenti, Giovanni Musci
In the last 20 years, several new genes and proteins involved in iron metabolism in eukaryotes, particularly related to pathological states both in animal models and in humans have been identified, and we are now starting to unveil at the molecular level the mechanisms of iron absorption, the regulation of iron transport and the homeostatic balancing processes. In this review, we will briefly outline the general scheme of iron metabolism in humans and then focus our attention on the cellular iron export system formed by the permease ferroportin and the ferroxidase ceruloplasmin...
February 16, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29452568/primary-cilia-regulated-transcriptome-in-the-renal-collecting-duct
#2
Sami G Mohammed, Francisco J Arjona, Eric H J Verschuren, Zeineb Bakey, Wynand Alkema, Sacha van Hijum, Miriam Schmidts, René J M Bindels, Joost G J Hoenderop
Renal tubular cells respond to mechanical stimuli generated by urinary flow to regulate the activity and transcript abundance of important genes for ion handling, cellular homeostasis, and proper renal development. The primary cilium, a mechanosensory organelle, is postulated to regulate this mRNA response. The aim of this study is to reveal the transcriptome changes of tubular epithelia in response to fluid flow and determine the role of primary cilia in this process. Inner-medullary collecting duct (CD) cells were subjected to either static or physiologically relevant fluid flow (∼0...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29452354/alpha-synuclein-inhibits-snx3-retromer-mediated-retrograde-recycling-of-iron-transporters-in-s-cerevisiae-and-c-elegans-models-of-parkinson-s-disease
#3
Dhaval Patel, Chuan Xu, Sureshbabu Nagarajan, Zhengchang Liu, Wayne O Hemphill, Runhua Shi, Vladimir N Uversky, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We probed the role of alpha-synuclein (α-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound multicopper ferroxidase, whose ferroxidase domain is orthologous to human ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then channel through the Ftr1 permease into the cell. When the concentration of external iron is low (< 1 µM), Fet3/Ftr1 is maintained on the plasma membrane by retrograde endocytic-recycling; whereas, when the concentration of external iron is high (> 10 µM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for degradation...
February 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29452096/the-macrophage-heme-heme-oxygenase-1-system-and-its-role-in-inflammation
#4
REVIEW
Vijith Vijayan, Frank A D T G Wagener, Stephan Immenschuh
Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO, plays a critical role in inflammation and iron homeostasis. Regulatory functions of HO-1 are mediated via the catalytic breakdown of heme, which is an iron-containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory effects. The HO reaction produces the antioxidant and anti-inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently converted into bilirubin, along with iron, which is reutilized for erythropoiesis...
February 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29452083/tribolium-castaneum-gene-expression-changes-after-paranosema-whitei-infection
#5
Alberto Lopez-Ezquerra, Andreas Mitschke, Erich Bornberg-Bauer, Gerrit Joop
BACKGROUND: Microsporidia are obligate parasites that possess some of the smallest eukaryotic genomes. Several insect species are susceptible to infections by microsporidian parasites. Paranosema whitei frequently infects young larvae of Tribolium castaneum and obligately kills the host whereupon transmission to subsequent hosts is accomplished via spores. P. whitei infection results in developmental arrest of T. castaneum, preventing larvae from pupation. The mechanisms underlying P...
February 13, 2018: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29435647/the-unique-fold-and-lability-of-the-2fe-2s-clusters-of-neet-proteins-mediate-their-key-functions-in-health-and-disease
#6
REVIEW
Ola Karmi, Henri-Baptiste Marjault, Luca Pesce, Paolo Carloni, Jose' N Onuchic, Patricia A Jennings, Ron Mittler, Rachel Nechushtai
NEET proteins comprise a new class of [2Fe-2S] cluster proteins. In human, three genes encode for NEET proteins: cisd1 encodes mitoNEET (mNT), cisd2 encodes the Nutrient-deprivation autophagy factor-1 (NAF-1) and cisd3 encodes MiNT (Miner2). These recently discovered proteins play key roles in many processes related to normal metabolism and disease. Indeed, NEET proteins are involved in iron, Fe-S, and reactive oxygen homeostasis in cells and play an important role in regulating apoptosis and autophagy. mNT and NAF-1 are homodimeric and reside on the outer mitochondrial membrane...
February 12, 2018: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29434930/increased-expression-of-hepcidin-and-associated-upregulation-of-jak-stat3-signaling-in-human-gastric-cancer
#7
Erdong Zuo, Ye Lu, Min Yan, Xiangtao Pan, Xu Cheng
Gastric cancer is one of the most common malignancies with high cancer-associated mortality rate globally. Hepcidin is the peptide hormone, which is critically important in the regulation of systemic iron homeostasis. Cumulating evidence has reported that the disturbed local expression of hepcidin may serve as a predictive biomarker in assessing the clinical outcomes in a range of cancer types. However, the expression profile of hepcidin in human gastric cancer is remains to be investigated. In the present retrospective study, using archived paraffin-embedded tissue blocks, the local production of hepcidin by immunohistochemical analysis was detected, and then its correlation with clinicopathological characteristics in human gastric cancer was evaluated...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432835/quercetin-and-iron-metabolism-what-we-know-and-what-we-need-to-know
#8
REVIEW
Lin Xiao, Gang Luo, Yuhan Tang, Ping Yao
Iron is a life-supporting micronutrient that is required in the human diet, and is essential for maintaining physiological homeostasis. Properly harnessing a redox-active metal such as iron is a great challenge for cells and organisms because an excess of highly reactive iron catalyzes the formation of reactive oxygen species and can lead to cell and tissue damage. Quercetin is a typical flavonoid that is commonly found in fruits and vegetables and has versatile biological effects. From a classical viewpoint, owing to its unique chemical characteristics, quercetin has long been associated with iron metabolism only in the context of its iron-chelating and ROS-scavenging activities...
February 9, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29430595/the-c19s-substitution-enhances-the-stability-of-hepcidin-while-conserving-its-biological-activity
#9
Edina Pandur, Zsuzsanna Fekete, Kitti Tamási, László Grama, Edit Varga, Katalin Sipos
Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level through its interaction with iron exporter ferroportin. Thus, hepcidin agonists provide a promising opportunity in the treatment of iron disorders caused by lacking or decreased hepcidin expression. We investigated the importance of each of the eight highly conserved cysteines for the biological activity of hepcidin. Eight cysteine mutants were created with site directed mutagenesis. The binding ability of these hepcidin mutants to the hepcidin receptor ferroportin was determined using bacterial two-hybrid system and WRL68 human hepatic cells...
February 12, 2018: Protein Journal
https://www.readbyqxmd.com/read/29427425/dissociation-between-iron-and-heme-biosynthesis-is-largely-accountable-for-respiration-defects-of-shewanella-oneidensis-fur-mutants
#10
Huihui Fu, Lulu Liu, Ziyang Dong, Shupan Guo, Haichun Gao
Iron, a major protein cofactor, is essential for most organisms but can be toxic simultaneously. Iron homeostasis thus has to be effectively maintained under a range of iron regimes. This may be particularly true with Shewanella oneidensis, a representative of dissimilatory metal-reducing bacteria (DMRB) capable of respiring a variety of chemicals as electron acceptors (EAs), including iron ores. Although iron respiration and its regulation have been extensively studied in this bacterium, how iron homeostasis is maintained remains largely unknown...
February 2, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29420779/the-mitochondrial-abc-transporter-atm1-plays-a-role-in-iron-metabolism-and-virulence-in-the-human-fungal-pathogen-cryptococcus-neoformans
#11
Eunsoo Do, Seho Park, Ming-Hui Li, Jia-Mei Wang, Chen Ding, James W Kronstad, Won Hee Jung
Iron-sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29418021/association-between-serum-hepcidin-level-and-restless-legs-syndrome
#12
Yves Dauvilliers, Sofiene Chenini, Jérôme Vialaret, Constance Delaby, Lily Guiraud, Audrey Gabelle, Regis Lopez, Christophe Hirtz, Isabelle Jaussent, Sylvain Lehmann
BACKGROUND: To better understand the role of iron homeostasis dysregulation in restless legs syndrome, we compared serum hepcidin and ferritin levels in drug-free patients with primary restless legs syndrome and healthy controls and studied the relationship between hepcidin level and restless legs syndrome severity. METHODS: One hundred and eight drug-free patients with primary restless legs syndrome (65 women; median age, 61.5 years) and 45 controls (28 women; median age, 53...
February 8, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29415739/hepcidin-an-emerging-and-important-player-in-brain-iron-homeostasis
#13
REVIEW
Driton Vela
Hepcidin is emerging as a new important factor in brain iron homeostasis. Studies suggest that there are two sources of hepcidin in the brain; one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain. The most important source of hepcidin in the brain are glial cells. Role of hepcidin in brain functions has been observed during neuronal iron-load and brain hemorrhage, where secretion of abundant hepcidin is related with the severity of brain damage...
February 7, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29409696/fur-regulation-of-staphylococcus-aureus-heme-oxygenases-is-required-for-heme-homeostasis
#14
Lisa J Lojek, Allison J Farrand, Andy Weiss, Eric P Skaar
Heme is a cofactor that is essential for cellular respiration and for the function of many enzymes. If heme levels become too low within the cell, S. aureus switches from producing energy via respiration to producing energy by fermentation. S. aureus encodes two heme oxygenases, IsdI and IsdG, which cleave the porphyrin heme ring releasing iron for use as a nutrient source. Both isdI and isdG are only expressed under low iron conditions and are regulated by the canonical Ferric Uptake Regulator (Fur). Here we demonstrate that unregulated expression of isdI and isdG within S...
February 1, 2018: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29407589/prognostic-implications-of-low-transferrin-saturation-in-patients-with-primary-myelofibrosis
#15
Marko Lucijanic, Zeljko Prka, Vlatko Pejsa, Tajana Stoos-Veic, Jelena Lucijanic, Rajko Kusec
OBJECTIVES: Transferrin saturation (TSAT) 20% or less is considered to represent functional iron deficiency in the context of malignant disease, phenomenon mediated through inflammatory changes of iron homeostasis. We aimed to investigate clinical and prognostic significance of low TSAT in patients with primary (PMF) and secondary myelofibrosis (SMF), malignant diseases characterized by strong inflammatory milieu. METHODS: We retrospectively analyzed 87 patients with myelofibrosis and compared TSAT with disease specific parameters...
January 29, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29407213/iron-released-from-reactive-microglia-by-noggin-improves-myelin-repair-in-the-ischemic-brain
#16
Jin A Shin, Yul A Kim, Hye Won Kim, Hee-Sun Kim, Kyung-Eun Lee, Jihee Lee Kang, Eun-Mi Park
We previously reported that the bone morphogenetic protein (BMP) antagonist, noggin, improved the repair process with an increase in the reactive microglia/macrophage population in the ischemic brain. Since BMP plays a role in intracellular iron homeostasis via the hepcidin/ferroportin axis, and iron is required for myelination, this study was aimed to determine whether noggin affected iron status and remyelination in the brain following ischemic stroke. We further examined the effect of blocking the BMP/hepcidin pathway on reactive microglia (BV2) and myelination of oligodendroglial cells (MO3...
January 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29402131/neurotoxicity-linked-to-dysfunctional-metal-ion-homeostasis-and-xenobiotic-metal-exposure-redox-signaling-and-oxidative-stress
#17
Carla Garza-Lombo, Yanahi Posadas, Liliana Quintanar, Maria E Gonsebatt, Rodrigo Franco
SIGNIFICANCE: Essential metals such as copper, iron, manganese and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our lifespan, humans are also exposed to xenobiotic metals from natural and anthropogenic sources including aluminum, arsenic, cadmium, lead and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals is linked to several neurological disorders including neurodegeneration and neurodevelopmental alterations...
February 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29396986/s-nitrosoglutathione-works-downstream-of-nitric-oxide-to-mediate-iron-deficiency-signaling-in-arabidopsis
#18
Sakthivel Kailasam, Ying Wang, Jing-Chi Lo, Hsin-Fang Chang, Kuo-Chen Yeh
Iron (Fe) is essential for plant growth and development. Knowledge of Fe signaling, from the beginning of perception to activation of the uptake process, is critical for crop improvement. Here, by using chemical screening, we identified a small molecule 3-amino-N-(3-methylphenyl)thieno[2,3-b]pyridine-2-carboxamide named R7 ("R" denoting repressor of IRON-REGULATED TRANSPORTER 1), that modulates Fe homeostasis of Arabidopsis. R7 treatment led to reduced Fe levels in plants, thus causing severe chlorosis under Fe deficiency...
February 3, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29394034/iron-and-its-role-in-cancer-defense-a-double-edged-sword
#19
Frank Thévenod
Iron (Fe) is an essential metal, vital for biological functions, including electron transport, DNA synthesis, detoxification, and erythropoiesis that all contribute to metabolism, cell growth, and proliferation. Interactions between Fe and O2 can result in the generation of reactive oxygen species (ROS), which is based on the ability of Fe to redox cycle. Excess Fe may cause oxidative damage with ensuing cell death, but DNA damage may also lead to permanent mutations. Hence Fe is carcinogenic and may initiate tumor formation and growth, and also nurture the tumor microenvironment and metastasis...
February 5, 2018: Metal Ions in Life Sciences
https://www.readbyqxmd.com/read/29394029/10-gallium-complexes-as-anticancer-drugs
#20
Christopher R Chitambar
Clinical trials have shown gallium nitrate, a group 13 (formerly IIIa) metal salt, to have antineoplastic activity against non-Hodgkin's lymphoma and urothelial cancers. Interest in gallium as a metal with anticancer properties emerged when it was discovered that 67Ga(III) citrate injected in tumor-bearing animals localized to sites of tumor. Animal studies showed non-radioactive gallium nitrate to inhibit the growth of implanted solid tumors. Following further evaluation of its efficacy and toxicity in animals, gallium nitrate, Ga(NO3)3, was designated an investigational drug by the National Cancer Institute (USA) and advanced to Phase 1 and 2 clinical trials...
February 5, 2018: Metal Ions in Life Sciences
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