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Iron metabolism

Xinxin Song, Yangchun Xie, Rui Kang, Wen Hou, Xiaofang Sun, Michael W Epperly, Joel S Greenberger, Daolin Tang
Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs...
October 20, 2016: Biochemical and Biophysical Research Communications
Jacob E Choby, Laura A Mike, Ameya A Mashruwala, Brendan F Dutter, Paul M Dunman, Gary A Sulikowski, Jeffrey M Boyd, Eric P Skaar
The rising problem of antimicrobial resistance in Staphylococcus aureus necessitates the discovery of novel therapeutic targets for small-molecule intervention. A major obstacle of drug discovery is identifying the target of molecules selected from high-throughput phenotypic assays. Here, we show that the toxicity of a small molecule termed '882 is dependent on the constitutive activity of the S. aureus virulence regulator SaeRS, uncovering a link between virulence factor production and energy generation. A series of genetic, physiological, and biochemical analyses reveal that '882 inhibits iron-sulfur (Fe-S) cluster assembly most likely through inhibition of the Suf complex, which synthesizes Fe-S clusters...
October 19, 2016: Cell Chemical Biology
Silvia Celletti, Youry Pii, Tanja Mimmo, Stefano Cesco, Stefania Astolfi
Plant mechanisms responding to iron (Fe) deficiency have been widely described; it is well known that Strategy II plants, as durum wheat, cope with this stress by increasing both the synthesis and secretion of phytosiderophores (PS). The important contribution of the sulfate assimilatory pathway has been also demonstrated to improve Fe use efficiency in several grasses, such as maize, barley and wheat, most likely because PS are produced from nicotianamine, whose precursor is methionine. Here, the physiological response of durum wheat (T...
October 13, 2016: Plant Physiology and Biochemistry: PPB
Xingkang Jiang, Changwen Zhang, Shiyong Qi, Shanqi Guo, Yue Chen, E Du, Hongtuan Zhang, Xiaoming Wang, Ranlu Liu, Baomin Qiao, Kuo Yang, Zhihong Zhang, Yong Xu
Although we and other studies indicated ZNF217 expression was increased in prostate cancer (PCa), the factors mediating its misregulated expression and their oncogenic activity remain largely unexplored. Recent evidence demonstrated that ferroportin (FPN) reduction lead to decreased iron export and increased intercellular iron that consequently aggravates the oncogenic effects of iron. In the present study, ZNF217 was identified as a transcriptional repressor that inhibits FPN expression. Increased of ZNF217 expression led to decreased FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth...
October 19, 2016: Oncotarget
Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Somayeh Atari-Hajipirloo, Neda Valizadeh, Mohammad-Hassan Khadem-Ansari, Yousef Rasmi, Fatemeh Kheradmand
BACKGROUND: The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. OBJECTIVES: The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated...
April 2016: International Journal of Endocrinology and Metabolism
Nicolas Leuenberger, Emanuele Bulla, Olivier Salamin, Raul Nicoli, Neil Robinson, Norbert Baume, Martial Saugy
The concentration of hepcidin, a key regulator of iron metabolism, is suppressed during periods of increased erythropoietic activity. The present study obtained blood samples from 109 elite athletes and examined the correlations between hepcidin and markers of erythropoiesis and iron metabolism (i.e., hemoglobin, erythropoietin (EPO), ferritin, erythroferrone (ERFE), and iron concentration). Furthermore, an administration study was undertaken to examine the effect of recombinant human EPO (rhEPO) delta (Dynepo™) on hepcidin concentrations in healthy male volunteers...
October 18, 2016: Drug Testing and Analysis
IJsbrand T Klip, Adriaan A Voors, Dorine W Swinkels, Stephan J L Bakker, Jenny E Kootstra-Ros, Carolyn S Lam, Pim van der Harst, Dirk J van Veldhuisen, Peter van der Meer
AIMS: Heart failure (HF) is a common manifestation of patients with primary and secondary causes of iron overload, whereas in patients with established HF iron deficiency impairs outcome. Whether iron stores, either depleted or in overload, amplify the risk for new-onset HF among healthy individuals is unknown. The present study aimed to assess whether markers of iron status or the iron-regulatory hormone hepcidin are associated with new-onset HF or cardiovascular (CV) events in the general population...
October 19, 2016: European Journal of Heart Failure
Antonino Baez, Joseph Shiloach
The damaging effect of high oxygen concentration on growth of Escherichia coli is well established. Over-oxygenation increases the intracellular concentration of reactive oxygen species (ROS), causing the destruction of the [4Fe-4S] cluster of dehydratases and limiting the biosynthesis of both branched-chain amino acids and nicotinamide adenine dinucleotide. A key enzyme that reduces the damaging effect of superoxide is superoxide dismutase (SOD). Its transcriptional regulation is controlled by global transcription regulators that respond to changes in oxygen and iron concentrations and pH...
October 18, 2016: Antonie Van Leeuwenhoek
Matthew B Lanktree, Bekim Sadikovic, John S Waye, Alexander Levstik, Bruce B Lanktree, Jovana Yudin, Mark A Crowther, Guillaume Pare, Paul C Adams
BACKGROUND: Next-generation sequencing of an iron metabolism gene panel could identify pathogenic mutations, improving on standard hemochromatosis genetic testing and providing a molecular diagnosis in patients with suspected iron overload. METHODS: A next-generation sequencing panel of 15 genes with known roles in iron metabolism was constructed. 190 patients were sequenced: 94 from a tertiary hemochromatosis clinic, and 96 submitted for HFE testing with biochemical evidence of iron overload [elevated ferritin (>450 μg/L) or transferrin saturation (>55%)] obtained from a chart review...
October 18, 2016: European Journal of Haematology
M L Mispireta, L E Caulfield, N Zavaleta, M Merialdi, D L Putnick, M H Bornstein, J A DiPietro
Zinc is an essential micronutrient for the development of the fetal renal, cardiovascular and metabolic systems; however, there is limited evidence of its effects on the postnatal cardiometabolic function. In this study, we evaluated the effect of maternal zinc supplementation during pregnancy on the cardiometabolic profile of the offspring in childhood. A total of 242 pregnant women were randomly assigned to receive a daily supplement containing iron+folic acid with or without zinc. A follow-up study was conducted when children of participating mothers were 4...
October 17, 2016: Journal of Developmental Origins of Health and Disease
Y Cedeño, M López-Alonso, M Miranda
OBJECTIVES: Defects in copper metabolism have been described in several dog breeds, and recently, it has been suggested that changes in other essential trace elements could be involved in the pathogenesis of hepatic disease. This study measured hepatic copper accumulation and its interactions with other essential trace and toxic metals in dogs diagnosed with chronic hepatitis. METHODS: Liver samples of 20 chronic hepatitis and 20 healthy dogs were collected. Samples were acid digested, and essential metals (cobalt, copper, iron, manganese, molibdenum, selenium and zinc) and toxic metals (arsenic, cadmium, mercury and lead) were analysed by inductively-coupled plasma mass spectrometry...
October 16, 2016: Journal of Small Animal Practice
Monika Kasztura, Magdalena Dzięgała, Kamil Kobak, Jacek Bania, Grzegorz Mazur, Waldemar Banasiak, Piotr Ponikowski, Ewa Anita Jankowska
: Background Iron is presumed to play an important role in functioning of cardiomyocytes and skeletal myocytes. There is scarcity of direct data characterizing the cells functioning when exposed to iron depletion or iron overload in cellular environment. There is some clinical evidence demonstrating that iron deficiency has serious negative prognostic consequence in heart failure (HF) patients and its correction brought clinical benefit. BACKGROUND: Iron is presumed to play an important role in functioning of cardiomyocytes and skeletal myocytes...
October 17, 2016: Kardiologia Polska
Ragnhild Reehorst Lereim, Eystein Oveland, Yichuan Xiao, Øivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Shao-Cong Sun, Frode S Berven
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak...
September 2016: Journal of Proteomics & Bioinformatics
Yuanyuan Chen, Jian Li, Jin Wei, Atufa Kawan, Li Wang, Xuezhen Zhang
Cyanobacterial blooms and their associated toxins pose a great threat to human beings. The situation is even worse for those whose drinking water source is a cyanotoxin-polluted water body. Therefore, efficient and safe treatments urgently need to be developed. The present study verified the application of vitamin C on the inhibition of toxic Microcystis aeruginosa. Our results showed that vitamin C drove the Fenton reaction and significantly sterilized cultures of M. aeruginosa. The algicidal activity of vitamin C was dependent on its involvement in iron (Fe) metabolism...
October 6, 2016: Journal of Hazardous Materials
Daria Chrobok, Simon R Law, Bastiaan Brouwer, Pernilla Lindén, Agnieszka Ziolkowska, Daniela Liebsch, Reena Narsai, Bozena Szal, Thomas Moritz, Nicolas Rouhier, James Whelan, Per Gardestrom, Olivier Keech
The functions of mitochondria during leaf senescence, a type of programmed cell death aiming at the massive retrieval of nutrients from the senescing organ to the rest of the plant, remain elusive. Here, combining experimental and analytical approaches, we showed that mitochondrial integrity is conserved until the latest stages of leaf senescence, while their number drops by 30%. Adenylate phosphorylation state assays and mitochondrial respiratory measurements indicated that the leaf energy status is also maintained during this time period...
October 15, 2016: Plant Physiology
Christina M Wyatt, Tilman B Drüeke
The treatment of anemia with erythropoiesis-stimulating agents and iron supplementation has become the standard of care in patients with chronic kidney disease. Because of the risks associated with this approach, hypoxia inducible factor stabilizing prolyl hydroxylase inhibitors were developed as a potential treatment alternative. In recent phase 2 trials, these agents raised hemoglobin in a predictable and controlled manner and improved markers of iron metabolism. More experience is needed to establish long-term efficacy, tolerability, and safety, and to determine whether their use is associated with lower iron requirements...
November 2016: Kidney International
Trey K Sato, Mary Tremaine, Lucas S Parreiras, Alexander S Hebert, Kevin S Myers, Alan J Higbee, Maria Sardi, Sean J McIlwain, Irene M Ong, Rebecca J Breuer, Ragothaman Avanasi Narasimhan, Mick A McGee, Quinn Dickinson, Alex La Reau, Dan Xie, Mingyuan Tian, Jennifer L Reed, Yaoping Zhang, Joshua J Coon, Chris Todd Hittinger, Audrey P Gasch, Robert Landick
The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically...
October 2016: PLoS Genetics
Débora Villaño, Cristina Vilaplana, Sonia Medina, Francisco Algaba-Chueca, Roberto Cejuela-Anta, Jose Miguel Martínez-Sanz, Federico Ferreres, Angel Gil-Izquierdo
The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of 120 days, measuring the hepcidin concentration in the plasma of 16 elite triathletes, and the effect of the ingestion of 200 mL of either aronia-citrus juice or a placebo drink for 45 days, in a crossover design. The highest plasma hepcidin concentrations were observed at the beginning of the study (116 ± 63 nM) and levels steadily decreased until the end of the intervention (final value 10 ± 7...
October 8, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jabadurai Jayapaul, Susanne Arns, Matt Bunker, Marek Weiler, Sandra Rutherford, Peter Comba, Fabian Kiessling
: Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated...
2016: Nano Research
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