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Iron homeostasis

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https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#1
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28819948/the-role-of-selenium-in-thyroid-gland-pathophysiology
#2
Michał Stuss, Marta Michalska-Kasiczak, Ewa Sewerynek
It is now assumed that proper functioning of the thyroid gland (TG), beside iodine, requires also a number of elements, including selenium, iron, zinc, copper, and calcium. In many cases, only an adequate supply of one of these microelements (e.g. iodine) may reveal symptoms resulting from deficits of other microelements (e.g. iron or selenium). Selenium is accounted to the trace elements of key importance for homeostasis of the human system, in particular, for the proper functioning of the immune system and the TG...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819251/g9a-regulates-breast-cancer-growth-by-modulating-iron-homeostasis-through-the-repression-of-ferroxidase-hephaestin
#3
Ya-Fang Wang, Jie Zhang, Yi Su, Yan-Yan Shen, Dong-Xian Jiang, Ying-Yong Hou, Mei-Yu Geng, Jian Ding, Yi Chen
G9a, a H3K9 methyltransferase, shows elevated expression in many types of human cancers, particularly breast cancer. However, the tumorigenic mechanism of G9a is still far from clear. Here we report that G9a exerts its oncogenic function in breast cancer by repressing hephaestin and destruction cellular iron homeostasis. In the case of pharmacological inhibition or short hairpin RNA interference-mediated suppression of G9a, the expression and activity of hephaestin increases, leading to the observed decrease of intracellular labile iron content and the disturbance of breast cancer cell growth in vitro and in vivo...
August 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28816060/the-broad-spectrum-antimicrobial-potential-of-mn-co-4-s2cnme-ch2co2h-a-water-soluble-co-releasing-molecule-corm-401-intracellular-accumulation-transcriptomic-and-statistical-analyses-and-membrane-polarization
#4
Lauren Katie Wareham, Samantha McLean, Ronald Begg, Namrata Rana, Salar Ali, John J Kendall, Guido Sanguinetti, Brian E Mann, Robert K Poole
AIMS: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. RESULTS: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28815688/bmp2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#5
Susanna Canali, Chia-Yu Wang, Kimberly B Zumbrennen-Bullough, Abraham Bayer, Jodie L Babitt
Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815214/chlamydomonas-reinhardtii-lfo1-is-an-isdg-family-heme-oxygenase
#6
Lisa J Lojek, Allison J Farrand, Jennifer H Wisecaver, Crysten E Blaby-Haas, Brian W Michel, Sabeeha S Merchant, Antonis Rokas, Eric P Skaar
Heme is essential for respiration across all domains of life. However, heme accumulation can lead to toxicity if cells are unable to either degrade or export heme or its toxic by-products. Under aerobic conditions, heme degradation is performed by heme oxygenases, enzymes which utilize oxygen to cleave the tetrapyrrole ring of heme. The HO-1 family of heme oxygenases has been identified in both bacterial and eukaryotic cells, whereas the IsdG family has thus far been described only in bacteria. We identified a hypothetical protein in the eukaryotic green alga Chlamydomonas reinhardtii, which encodes a protein containing an antibiotic biosynthesis monooxygenase (ABM) domain consistent with those associated with IsdG family members...
July 2017: MSphere
https://www.readbyqxmd.com/read/28811866/preliminary-data-on-the-interaction-between-some-biometals-and-oxidative-stress-status-in-mild-cognitive-impairment-and-alzheimer-s-disease-patients
#7
Ioana-Miruna Balmuș, Stefan-Adrian Strungaru, Alin Ciobica, Mircea-Nicusor Nicoara, Romeo Dobrin, Gabriel Plavan, Cristinel Ștefănescu
Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer's disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28798083/hamp1-mrna-and-plasma-hepcidin-levels-are-influenced-by-sex-and-strain-but-don-t-predict-tissue-iron-levels-in-inbred-mice
#8
Stela McLachlan, Kathryn E Page, Seung-Min Lee, Alex Loguinov, Erika Valore, Simon T Hui, Grace Jung, Jie Zhou, Aldons J Lusis, Brie Fuqua, Tomas Ganz, Elizabeta Nemeth, Chris D Vulpe
Iron homeostasis is tightly regulated and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex and strain dependent differences in mRNA and serum levels of hepcidin. Similarly, conflicting data on the relationship between hepcidin (Hamp1) mRNA levels and iron status as assessed by transferrin saturation and tissue iron concentrations were reported. Our aim was to clarify the relationships between strain, sex and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28796976/-hfeprotein-impact-on-iron-metabolism
#9
Barbara Kaczorowska-Hać, Jan Jacek Kaczor
Hereditary hemochromatosis type 1 is an autosomal recessive disorder caused by HFE gene mutations, which is an iron homeostasis metabolism controlling co-factor. Adults with male predomination present with clinical symptoms derived by iron overload in organs. The phenotype expression is individual with an influence of individual and environmental factors. Despite the fact that HFE variants are widespread, its impact still remains unknown. The article reviews the literature considering the role of HFE gene mutations regarding its impact in children...
2017: Developmental Period Medicine
https://www.readbyqxmd.com/read/28795681/-research-progress-of-iron-metabolism-in-critical-ill-patients
#10
Ling Xie, Shengnan Wang, Suyue Pan
Iron is an essential nutrient element for human, but has potential toxicity. Under physiological conditions, the processes of iron absorption, transportation, cellular uptake and utilization, storage, release, excretion as well as regulation of iron metabolism maintain the iron homeostasis. However under pathological conditions, the iron metabolism changes and is associated with the pathological states. In order to realize the relationship between the critical illness status and the iron metabolism, we start with an analysis of the basic processes of iron metabolism in human and the toxicity of iron, followed by summary on the alteration of iron metabolism in the settings of pathological conditions, such as inflammation, infection and anemia, which often occur in critical illness...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28794014/iron-affects-ire1-clustering-propensity-and-the-amplitude-of-endoplasmic-reticulum-stress-signaling
#11
Nir Cohen, Michal Breker, Anush Bakunts, Kristina Pesek, Ainara Chas, Josepmaria Argemí, Andrea Orsi, Lihi Gal, Silvia Chuartzman, Yoav Wigelman, Felix Jonas, Peter Walter, Robert Ernst, Tomás Aragón, Eelco van Anken, Maya Schuldiner
The unfolded protein response (UPR) allows cells to adjust secretory pathway capacity according to need. Ire1, the endoplasmic reticulum (ER) stress sensor and central activator of the UPR is conserved from the budding yeast Saccharomyces cerevisiae to humans. Under ER stress conditions, Ire1 clusters into foci that enable optimal UPR activation. To discover factors that affect Ire1 clustering, we performed a high-content screen using a whole-genome yeast mutant library expressing Ire1-mCherry. We imaged the strains following UPR induction and found 154 strains that displayed alterations in Ire1 clustering...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28793787/the-roles-of-nrf2-in-modulating-cellular-iron-homeostasis
#12
Michael John Kerins, Aikseng Ooi
SIGNIFICANCE: Iron and oxygen are intimately linked: iron is an essential nutrient utilized as a cofactor in enzymes for oxygen transport, oxidative phosphorylation, and metabolite oxidation. However, excess labile iron facilitates the formation of oxygen-derived free radicals capable of damaging biomolecules. Therefore, biological utilization of iron is a tightly regulated process. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor, which can respond to oxidative and electrophilic stress, regulates several genes involved in iron metabolism...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28793778/peroxiredoxin-2-a-novel-regulator-of-iron-homeostasis-in-ineffective-erythropoiesis
#13
Alessandro Matte, Luigia De Falco, Enrica Federti, Anna Cozzi, Achille Iolascon, Sonia Levi, Narla Mohandas, Alberto Zamo, Mariasole Bruno, Christophe Leboeuf, Anne Janin, Angela Siciliano, Thomas Ganz, Giorgia Federico, Francesca Carlomagno, Sebastian Mueller, Ines Silva, Carmine Carbone, Davide Melisi, D W Kim, Soo Young Choi, Lucia DE Franceschi
AIMS: Iron-overload (IO) is a life-threatening complication of chronic hemolytic disorders such as β-thalassemia. IO results in severe cellular oxidative damage, leading to organ failure. Peroxiredoxin-2 (Prx2), a typical 2-cysteine-(Cys)-peroxiredoxin, is an important component of cyto-protective system, but its response to IO is still to be fully defined. RESULTS: We studied the effects of IO on Prx2-knockout mice (Prx2-/-). The absence of Prx2 enhanced toxicity due to IO on erythropoiesis...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28792913/iron-in-neurodegenerative-disorders-being-in-the-wrong-place-at-the-wrong-time
#14
Sotirios Apostolakis, Anna-Maria Kypraiou
Brain iron deposits have been reported consistently in imaging and histologic examinations of patients with neurodegenerative disorders. While the origins of this finding have not been clarified yet, it is speculated that impaired iron homeostasis or deficient transport mechanisms result in the accumulation of this highly toxic metal ultimately leading to formation of reactive oxygen species and cell death. On the other hand, there are also those who support that iron is just an incidental finding, a by product of neuronal loss...
August 9, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28792693/serum-hepcidin-levels-in-multiple-myeloma
#15
Manolov Victor, Hadjiev Evgeniy, Tzvetkova Gergana, Petrova Julia, Vasilev Vasil, Marinov Borislav, Bogov Ivo, Gramatikova Zlatina, Tzatchev Kamen
BACKGROUND: Multiple myeloma (MM) is a malignant disease with a 10% frequency among all haematology neoplasms. It is characterized by clone proliferation of plasmatic cells in bone marrow, monoclonal gammopathy, and anemia, hypercalcemia, and kidney failure and bone lesions. IL-6 is an inflammatory cytokine, potential growth factor for myeloma cells, as elevated serum levels are connected with poor disease prognosis. IL-6 modulates many gene transcriptions, encoding synthesis of acute phase proteins, including C-reactive protein (CRP) and hepcidin...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28790810/indices-of-iron-homeostasis-correlate-with-airway-obstruction-in-an-nhanes-iii-cohort
#16
Andrew J Ghio, Elizabeth D Hilborn
Cigarette smoking results in the accumulation of iron both systemically and locally, in the lung thereby causing imbalance in iron homeostasis. This disruption in iron homeostasis can be associated with oxidative stress and consequent tissue injury. Therefore, in this study, we tested the association between iron homeostasis and airway obstruction by examining a large cohort of smokers and non-smokers for relationships between 1) serum ferritin and iron concentrations and transferrin saturation and 2) forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and their ratio (FEV1/FVC)...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28782591/mitochondrial-dysfunction-in-the-neuro-degenerative-and-cardio-degenerative-disease-friedreich-s-ataxia
#17
Shannon Chiang, Danuta S Kalinowski, Patric J Jansson, Des R Richardson, Michael L-H Huang
Mitochondrial homeostasis is essential for maintaining healthy cellular function and survival. The detrimental involvement of mitochondrial dysfunction in neuro-degenerative diseases has recently been highlighted in human conditions, such as Parkinson's, Alzheimer's and Huntington's disease. Friedreich's ataxia (FA) is another neuro-degenerative, but also cardio-degenerative condition, where mitochondrial dysfunction plays a crucial role in disease progression. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism...
August 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28780484/expression-of-hepcidin-and-ferroportin-in-full-term-placenta-of-pregnant-cows
#18
Sante Roperto, Valeria Russo, Chiara Urraro, Anna Cutarelli, Antonella Perillo, Francesca De Falco, Franco Roperto
Hepcidin (HEP) and ferroportin (FPN) play a central role in systemic iron homeostasis. The HEP/FPN axis controls both extracellular iron concentration and total body iron levels. HEP is synthesized mainly by hepatocytes and controls the absorption of dietary iron and the distribution of iron to the various cell types; its synthesis is regulated by both iron and innate immunity. FPN is a membrane protein and the major exporter of iron from mammalian cells, including iron recycling macrophages, iron absorbing duodenal enterocytes, and iron storing hepatocytes...
July 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/28775066/the-interplay-between-iron-and-oxygen-homeostasis-with-a-particular-focus-on-the-heart
#19
Samira Lakhal-Littleton, Peter A Robbins
Iron is subject to tight homeostatic control in mammals. At the systemic level, iron homeostasis is controlled by the liver-derived hormone hepcidin acting on its target ferroportin in the gut, spleen and liver, which form the sites of iron uptake, recycling and storage, respectively. At the cellular level, iron homeostasis is dependent on the iron regulatory proteins IRP1/IRP2. Unique chemical properties of iron underpin its importance in biochemical reactions involving oxygen. As such, it is not surprising that there are reciprocal regulatory links between iron and oxygen homeostasis, operating both at the systemic and cellular levels...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28774878/the-actin-binding-protein-profilin-2-is-a-novel-regulator-of-iron-homeostasis
#20
Sara Luscieti, Bruno Galy, Lucia Gutierrez, Michael Reinke, Jorge Couso, Maya Shvartsman, Antonio Di Pascale, Walter Witke, Matthias W Hentze, Pietro Pilo Boyl, Mayka Sanchez
Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target mRNAs. We identified the profilin2 (Pfn2) mRNA, which encodes an actin binding protein involved in endocytosis and neurotransmitters release, as a novel IRP-interacting transcript and studied its role in iron metabolism. Combination of EMSA experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA...
August 3, 2017: Blood
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