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Iron homeostasis

Brian Chiou, Emma H Neal, Aaron B Bowman, Ethan S Lippmann, Ian A Simpson, James R Connor
Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Duomeng Yang, Junmin Xi, Yun Xing, Xiangxu Tang, Xiaomeng Dai, Kaiying Li, Hongmei Li, Xiuxiu Lv, Daxiang Lu, Huadong Wang
BACKGROUND: Neonatal rat ventricular myocytes (NRVMs) have proven to be an ideal research model for cardiac disease. However, the current methods to purify NRVMs have a limitation to obtain high purity. The purpose of this study was to develop a NRVM purification method by using superparamagnetic iron oxide particles (SIOP). METHODS: NRVMs were purified by using SIOP (SIOP group). The differential attachment with or without bromodeoxyuridine (BrdU) treatment served as control and BrdU groups, respectively...
June 3, 2018: International Journal of Cardiology
Sandra Peherstorfer, Hans Henning Brewitz, Ajay Abisheck Paul George, Amelie Wißbrock, Jana Maria Adam, Lutz Schmitt, Diana Imhof
BACKGROUND: Tight regulation of heme homeostasis is a critical mechanism in pathogenic bacteria since heme functions as iron source and prosthetic group, but is also toxic at elevated concentrations. Hemolysin-activating lysine-acyltransferase (HlyC) from Escherichia coli is crucial for maturation of hemolysin A, which lyses several mammalian cells including erythrocytes liberating large amounts of heme for bacterial uptake. A possible impact and functional consequences of the released heme on events employing bacterial HlyC have remained unexplored...
June 14, 2018: Biochimica et Biophysica Acta
Maria Fernanda Laranjeira-Silva, Wanpeng Wang, Tamika K Samuel, Fernando Y Maeda, Vladimir Michailowsky, Iqbal Hamza, Zhongchi Liu, Norma W Andrews
Iron is essential for many cellular processes, but can generate highly toxic hydroxyl radicals in the presence of oxygen. Therefore, intracellular iron accumulation must be tightly regulated, by balancing uptake with storage or export. Iron uptake in Leishmania is mediated by the coordinated action of two plasma membrane proteins, the ferric iron reductase LFR1 and the ferrous iron transporter LIT1. However, how these parasites regulate their cytosolic iron concentration to prevent toxicity remains unknown...
June 15, 2018: PLoS Pathogens
Latha Ramakrishnan, Sofia L Pedersen, Quezia K Toe, Gregory J Quinlan, Stephen J Wort
The interplay between iron and oxygen is longstanding and central to all aerobic life. Tight regulation of these interactions including homeostatic regulation of iron utilization ensures safe usage of this limited resource. However, when control is lost adverse events can ensue, which are known to contribute to an array of disease processes. Recently, associations between disrupted iron homeostasis and pulmonary artery hypertension (PAH) have been described with the suggestion that there is a contributory link with disease...
2018: Frontiers in Physiology
Changhwan Ahn, Jong-Sam Choi, Eui-Bae Jeung
Transmembrane cation channels include those for calcium, copper and iron ion transport. Each channel has physiological significance, and all have been associated with disease. However, the comparative study of transcriptional‑translational levels in canine organs has not been previously reported. In the present study, organ‑specific expression of calcium channels, including sodium/potassium/calcium exchanger 3 (NCKX3) and transient receptor potential cation channel subfamily V member 2 (TRPV2), copper channels, including high affinity copper uptake protein 1 (CTR1) and copper‑transporting ATPase 1 (ATP7A), and iron channels, including iron‑regulated transporter 1 (IREG1) and hephaestin (HEPH) proteins and their mRNAs were examined in the canine duodenum, kidney, spleen and liver...
June 7, 2018: Molecular Medicine Reports
Mauricio Gomez-Gallardo, Luis A Sánchez, Alma L Díaz-Pérez, Christian Cortés-Rojo, Jesús Campos-García
The related study has confirmed that in Saccharomyces cerevisiae , iba57 protein participates in maturation of the [2Fe-2S] cluster into the Rieske protein, which plays important roles in the conformation and functionality of mitochondrial supercomplexes III/IV in the electron transport chain (Sánchez et al., 2018) [1]. We determined in S. cerevisiae the effects of mutation in the IBA57 gene on reactive oxygen species (ROS) and iron homeostasis. Flow cytometry and confocal microscopy analyses showed an increased generation of ROS, correlated with free Fe2+ release in the IBA57 mutant yeast...
June 2018: Data in Brief
Paulina López, Andrea Castro, Martha Flórez, Karen Miranda, Pilar Aranda, Cristina Sánchez-González, Juan Llopis, Miguel Arredondo
Obesity is characterized by mild chronic inflammation that is linked with impaired iron homeostasis. Studies in human and murine show that there is a transgenerational epigenetic inheritance via the gametes in obesity; however, there is little information on changes in the expression of microRNAs related to inflammation and iron homeostasis in spermatozoa from obese subjects. The present study investigated the expression of microRNAs related to inflammation (miR-21 y miR-155) and iron nutrition (miR-122 and miR-200b) in plasma, peripheral blood mononuclear cells (PBMC) and spermatozoa from normozoospermic controls (Cn; n = 17; BMI: 24...
2018: Frontiers in Genetics
Marilda da Cruz Fernandes, Antônio Generoso Severino, Adriana Maria Zago, Lucas Tortorelli, Fabiano B Carvalho, Felipe Luis Schneider
The role of the choroid plexus (CP) in iron (Fe) homeostasis has been suggested as the main mechanism of Fe uptake and storage in the mammalian central nervous system. Thus, the CP of the lateral and fourth ventricles was studied in guinea pigs with light and electron microscopy using methods including Perls' Prussian blue and Gomori acid phosphatase staining, immunoreactivity for ferritin and transferrin, as well as energy dispersive spectrometry microanalysis. The present study reveals the presence of endogenous Fe in CP epithelial cells...
September 2018: Journal of Trace Elements in Medicine and Biology
Fatemeh Sadat Alavi, Mahin Gheidi, Mansour Zahedi, Nasser Safari, Ulf Ryde
Heme degradation by heme oxygenase enzymes is important for maintaining iron homeostasis and prevention of oxidative stress. Previous studies have reported that heme degradation proceeds through three consecutive steps of O2 activation: the regiospecific self-hydroxylation of heme, the conversion of hydroxyheme to verdoheme and CO, and the cleavage of the verdoheme macrocycle to release biliverdin and free ferrous iron. Our results indicate that in the second step of heme degradation, not only verdoheme is generated but ring opening and biliverdin production also occur...
June 12, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Min Chen, Jiashuo Zheng, Guohao Liu, En Xu, Junzhuo Wang, Brie K Fuqua, Chris D Vulpe, Gregory J Anderson, Huijun Chen
Little is known about the iron efflux from the pancreas, but it is likely that multicopper ferroxidases (MCFs) are involved in this process. We thus used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout mice and Heph/Cp double-knockout mice to investigate the roles of MCFs in pancreatic iron homeostasis. We found that both HEPH and CP were expressed in the mouse pancreas, and that ablation of either MCF had limited effect on the pancreatic iron levels. However, ablation of both MCFs together led to extensive pancreatic iron deposition and severe oxidative damage...
May 31, 2018: Redox Biology
Martin Mangold, Michael Gütschow, Marit Stirnberg
Matriptase-2 is a type II transmembrane serine protease and a key regulator of systemic iron homeostasis. Since the activation mechanism and several features of the physiological role of matriptase-2 are not fully understood, there is strong need for analytical tools to perform tasks such as distinguishing active and inactive matriptase-2. For this purpose we present a short biotinylated peptide derivative with a chloromethyl ketone group, biotin-RQRR-CMK, as an activity-based probe for matriptase-2. Biotin-RQRR-CMK was kinetically characterized and exhibited a second-order rate constant of inactivation ( k inac / K i ) of 10,800 M−1 s−1 towards the matriptase-2 activity in the supernatant of transfected human embryonic kidney (HEK) cells...
May 21, 2018: Pharmaceuticals
Rozalynne Samira, Baohua Li, Daniel Kliebenstein, Chunying Li, Eric Davis, Jeffrey W Gillikin, Terri A Long
ILR3 and PYE function in a regulatory network that modulates GLS accumulation under iron deficiency. The molecular processes involved in the cross talk between iron (Fe) homeostasis and other metabolic processes in plants are poorly understood. In Arabidopsis thaliana the transcription factor IAA-LEUCINE RESISTANT3 (ILR3) regulates iron deficiency response, aliphatic glucosinolate (GLS) biosynthesis and pathogen response. ILR3 is also known to interact with its homolog, POPEYE (PYE), which also plays a role in Fe response...
June 7, 2018: Plant Molecular Biology
Laurence Britton, Kim Bridle, Janske Reiling, Nishreen Santrampurwala, Leesa Wockner, Helena Ching, Katherine Stuart, V Nathan Subramaniam, Gary Jeffrey, Tim St Pierre, Michael House, Joel Gummer, Robert Trengove, John Olynyk, Darrell Crawford, Leon Adams
Rodent and cell-culture models support a role for iron-related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD...
June 2018: Hepatology Communications
Mohammad A Kaisar, Farzane Sivandzade, Aditya Bhalerao, Luca Cucullo
It is well established that tobacco smoking is associated with vascular endothelial dysfunction in a causative and dose dependent manner primarily related to the tobacco smoke (TS) content of reactive oxygen species (ROS), nicotine, and oxidative stress (OS) -driven inflammation. Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes (e-Cigs) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury. Likewise, chronic e-Cig vaping could be prodromal to vascular endothelial dysfunctions...
June 4, 2018: Neuroscience Letters
Yang Su, Jie Chen, Ying Huang
Pentatricopeptide repeat (PPR) proteins are major players in mitochondrial and chloroplast RNA metabolism which is essential for normal organellar function. The fission yeast Schizosaccharomyces pombe has ten PPR proteins. We have previously reported that loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis leading to accumulation of reactive oxygen species and apoptotic cell death. In the present study, we show that loss of ppr3, ppr4, ppr6, or ppr10 can cause non-sexual flocculation and filamentous growth of cells...
June 6, 2018: FEMS Microbiology Letters
Adel A Hagag, Ibrahim M Badraia, Mohamed M Abdelmageed, Nahed M Hablas, Sahar Me Hazzaa, Nahla A Nosair
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the commonest childhood cancer. Transferrin receptor 1 (CD71) is a trans-membrane glycoprotein which has important role in iron homeostasis by acting as a gatekeeper regulating iron uptake from transferrin and is an attractive target for anti-cancer agents, particularly those that aim to induce lethal iron deprivation in malignant hematopoietic cells. AIM OF THE WORK: To assess the prognostic value of Transferrin receptor -1 (CD71) in children with newly diagnosed ALL...
June 4, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Pengcheng Sun, Song Wang, Jian Wang, Jing Sun, Min Peng, Ping Shi
Chemerin exhibits a tumor-inhibitory role in hepatocellular carcinoma. However, the effect of chemerin on essential metal elements in hepatic cells remains unclear. In our study, the contents of six important metal ions, including potassium, calcium, sodium, magnesium, iron and zinc, were detected in human hepatoma SMMC7721 and immortal hepatic QSG7701 cells by ICP-AES. The data showed that chemerin only decreases the content of intracellular iron in SMMC7721 cells. The reduction was due to the blockage of iron entry through the decrease in the mRNA levels of divalent metal transporter 1, iron regulatory proteins and transferrin receptors...
June 6, 2018: Metallomics: Integrated Biometal Science
Jiayou Wang, Noah Kainrad, Hong Shen, Zhou Zhou, Paula Rote, Yanqiao Zhang, Laura E Nagy, Jiashin Wu, Min You
Aberrant pre-mRNA splicing plays a pivotal role in liver diseases. However, roles of splicing regulators in alcoholic liver disease are unknown. Here, we investigated a splicing regulator Slu7 in the development of alcoholic steatohepatitis. Adenovirus (Ad)-mediated alteration of hepatic Slu7 expression in mice pair-fed either with or without (as control) ethanol in their diet was utilized. Knockdown of hepatic Slu7 by Ad-Slu7shRNA treatment ameliorated inflammation and attenuated liver injury in mice after ethanol administration...
June 2, 2018: American Journal of Pathology
Mikhail A Eldarov, Alexey V Beletsky, Tatiana N Tanashchuk, Svetlana A Kishkovskaya, Nikolai V Ravin, Andrey V Mardanov
Flor yeast strains represent a specialized group of Saccharomyces cerevisiae yeasts used for biological wine aging. We have sequenced the genomes of three flor strains originated from different geographic regions and used for production of sherry-like wines in Russia. According to the obtained phylogeny of 118 yeast strains, flor strains form very tight cluster adjacent to the main wine clade. SNP analysis versus available genomes of wine and flor strains revealed 2,270 genetic variants in 1,337 loci specific to flor strains...
2018: Frontiers in Microbiology
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