Intracellular Iron Storage and Biomineralisation

2009 ◽  
pp. 183-222 ◽  
Keyword(s):  
Intracellular Iron ◽  
Iron Storage

Iron storage sites in the myocardium as revealed by cytohistochemistry

1988 ◽  
Vol 46 ◽  
pp. 394-395
Author(s):  
M. Ashraf ◽  
F. Thompson ◽  
S. Miki ◽  
P. Srivastava
Keyword(s):  
Cardiac Tissue ◽  
Coronary Perfusion ◽  
Intracellular Iron ◽  
Ether Anesthesia ◽  
Intense Staining ◽  
Iron Storage ◽  
Thin Sections ◽  
Rat Hearts ◽  
Cacodylate Buffer ◽  
Made In

Iron is believed to play an important role in the pathogenesis of ischemic injury. However, the sources of intracellular iron in myocytes are not yet defined. In this study we have attempted to localize iron at various cellular sites of the cardiac tissue with the ferrocyanide technique.Rat hearts were excised under ether anesthesia. They were fixed with coronary perfusion with 3% buffered glutaraldehyde made in 0.1 M cacodylate buffer pH 7.3. Sections, 60 μm in thickness, were cut on a vibratome and were incubated in the medium containing 500 mg of potassium ferrocyanide in 49.5 ml H2O and 0.5 ml concentrated HC1 for 30 minutes at room temperature. Following rinses in the buffer, tissues were dehydrated in ethanol and embedded in Spurr medium.The examination of thin sections revealed intense staining or reaction product in peroxisomes (Fig. 1).

scholarly journals Adipose Tissue Expansion by Overfeeding Healthy Men Alters Iron Gene Expression

2018 ◽  
Vol 104 (3) ◽  
pp. 688-696 ◽  
Author(s):  
Berenice Segrestin ◽  
José Maria Moreno-Navarrete ◽  
Kevin Seyssel ◽  
Maud Alligier ◽  
Emmanuelle Meugnier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Serum Iron ◽  
Tissue Expansion ◽  
Lipid Storage ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Gene Encoding ◽  
Iron Storage ◽  
Healthy Men

Abstract Context Iron overload has been associated with greater adipose tissue (AT) depots. We retrospectively studied the potential interactions between iron and AT during an experimental overfeeding in participants without obesity. Methods Twenty-six participants (mean body mass index ± SD, 24.7 ± 3.1 kg/m2) underwent a 56-day overfeeding (+760 kcal/d). Serum iron biomarkers (ELISA), subcutaneous AT (SAT) gene expression, and abdominal AT distribution assessed by MRI were analyzed at the beginning and the end of the intervention. Results Before intervention: SAT mRNA expression of the iron transporter transferrin (Tf) was positively correlated with the expression of genes related to lipogenesis (lipin 1, ACSL1) and lipid storage (SCD). SAT expression of the ferritin light chain (FTL) gene, encoding ferritin (FT), an intracellular iron storage protein, was negatively correlated to SREBF1, a gene related to lipogenesis. Serum FT (mean, 92 ± 57 ng/mL) was negatively correlated with the expression of SAT genes linked to lipid storage (SCD, DGAT2) and to lipogenesis (SREBF1, ACSL1). After intervention: Overfeeding led to a 2.3 ± 1.3-kg weight gain. In parallel to increased expression of lipid storage–related genes (mitoNEET, SCD, DGAT2, SREBF1), SAT Tf, SLC40A1 (encoding ferroportin 1, a membrane iron export channel) and hephaestin mRNA levels increased, whereas SAT FTL mRNA decreased, suggesting increased AT iron requirement. Serum FT decreased to 67 ± 43 ng/mL. However, no significant associations between serum iron biomarkers and AT distribution or expansion were observed. Conclusion In healthy men, iron metabolism gene expression in SAT is associated with lipid storage and lipogenesis genes expression and is modulated during a 56-day overfeeding diet.

Tumor Cell Cytotoxicity of a Novel Metal Chelator

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1384-1389 ◽  
Author(s):  
S.V. Torti ◽  
F.M. Torti ◽  
S.P. Whitman ◽  
M.W. Brechbiel ◽  
G. Park ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Metal Chelator ◽  
Pendant Arm ◽  
Ferritin Synthesis ◽  
Bladder Cancer Cells ◽  
Sterically Hindered ◽  
American Society

Abstract We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 μmol/L compared with 70 μmol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration. © 1998 by The American Society of Hematology.

scholarly journals Ferricrocin, a Siderophore Involved in Intra- and Transcellular Iron Distribution in Aspergillus fumigatus

2009 ◽  
Vol 75 (12) ◽  
pp. 4194-4196 ◽  
Author(s):  
Anja Wallner ◽  
Michael Blatzer ◽  
Markus Schrettl ◽  
Bettina Sarg ◽  
Herbert Lindner ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Acquisition ◽  
Iron Starvation ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Essential Metal ◽  
Iron Distribution ◽  
Iron Transporter

ABSTRACT Iron is an essential metal for virtually all organisms. Iron acquisition is well characterized for various organisms, whereas intracellular iron distribution is poorly understood. In contrast to bacteria, plants, and animals, most fungi lack ferritin-mediated iron storage but possess an intracellular siderophore shown to be involved in iron storage. Here we demonstrate that deficiency in the intracellular siderophore ferricrocin causes iron starvation in conidia of Aspergillus fumigatus, demonstrating that ferricrocin is also involved in intra- and transcellular iron distribution. Thus, ferricrocin represents the first intracellular iron transporter identified in any organism.

scholarly journals Nifedipine Potentiates Susceptibility of Salmonella Typhimurium to Different Classes of Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1200
Author(s):  
David Haschka ◽  
Manuel Grander ◽  
Johannes Eibensteiner ◽  
Stefanie Dichtl ◽  
Sabine Koppelstätter ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Bacterial Resistance ◽  
Additive Effect ◽  
Lipocalin 2 ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Cellular Iron ◽  
Essential Nutrient ◽  
Conventional Antibiotics ◽  
Significant Additive Effect

The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse macrophage cell line RAW267.4, infected with the intracellular bacterium Salmonella Typhimurium, and exposed the cells to varying concentrations of nifedipine and/or ampicillin, azithromycin and ceftriaxone. We observed a significant additive effect of nifedipine in combination with various antibiotics, which was not observed when using Salmonella, with defects in iron uptake. Of interest, increasing intracellular iron levels increased the bacterial resistance to treatment with antibiotics or nifedipine or their combination. We further showed that nifedipine increases the expression of the siderophore-binding peptide lipocalin-2 and promotes iron storage within ferritin, where the metal is less accessible for bacteria. Our data provide evidence for an additive effect of nifedipine with conventional antibiotics against Salmonella, which is partly linked to reduced bacterial access to iron.

scholarly journals Iron storage in ferritin following intracellular hemoglobin denaturation in erythroleukemic cells

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 928-930 ◽  
Author(s):  
E Fibach ◽  
ER Bauminger ◽  
AM Konijn ◽  
S Ofer ◽  
EA Rachmilewitz
Keyword(s):  
Cell Lines ◽  
Storage Protein ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Cellular Iron ◽  
Ferritin Iron ◽  
Induction Of Differentiation ◽  
K 562 Cells ◽  
Murine Erythroleukemia ◽  
Erythroleukemic Cells

Abstract Murine erythroleukemia (MEL) and human K-562 cell lines were cultured in the presence of 57Fe, and the quantities of cellular iron-containing compounds were determined with the aid of Mossbauer spectroscopy. Upon induction of differentiation, both ferritin-iron and hemoglobin (Hb) iron could be detected. Treatment of the cells with 0.01%-0.02% acetylphenylhydrazine (APH) resulted in gradual denaturation of Hb and incorporation of the released Hb-iron into ferritin. Following treatment with APH, the ratio of Hb-57Fe to ferritin-57Fe decreased from 2.6 to 0.2 in MEL cells and from 0.56 to 0.12 in K-562 cells. No change was observed in the total intracellular iron. Using fluorescence ELISA, an increased level of immunologically detectable ferritin was found in hemoglobinized K-562 cells treated with APH, as compared to the amount of ferritin found in untreated cells. Ferritin may thus function not only as an intermediate during Hb synthesis, but also as storage protein for iron released during Hb denaturation.

scholarly journals Bacterioferritin: a key iron storage modulator that affects strain growth and butenyl-spinosyn biosynthesis in Saccharopolyspora pogona

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jianli Tang ◽  
Zirong Zhu ◽  
Haocheng He ◽  
Zhudong Liu ◽  
Ziyuan Xia ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Quantitative Proteomics ◽  
Polyketide Synthase ◽  
Storage Capacity ◽  
Oxidative Stress Response ◽  
Iron Toxicity ◽  
Intracellular Iron ◽  
Proteomics Analysis ◽  
Iron Storage

Abstract Background Butenyl-spinosyn, produced by Saccharopolyspora pogona, is a promising biopesticide due to excellent insecticidal activity and broad pesticidal spectrum. Bacterioferritin (Bfr, encoded by bfr) regulates the storage and utilization of iron, which is essential for the growth and metabolism of microorganisms. However, the effect of Bfr on the growth and butenyl-spinosyn biosynthesis in S. pogona has not been explored. Results Here, we found that the storage of intracellular iron influenced butenyl-spinosyn biosynthesis and the stress resistance of S. pogona, which was regulated by Bfr. The overexpression of bfr increased the production of butenyl-spinosyn by 3.14-fold and enhanced the tolerance of S. pogona to iron toxicity and oxidative damage, while the knockout of bfr had the opposite effects. Based on the quantitative proteomics analysis and experimental verification, the inner mechanism of these phenomena was explored. Overexpression of bfr enhanced the iron storage capacity of the strain, which activated polyketide synthase genes and enhanced the supply of acyl-CoA precursors to improve butenyl-spinosyn biosynthesis. In addition, it induced the oxidative stress response to improve the stress resistance of S. pogona. Conclusion Our work reveals the role of Bfr in increasing the yield of butenyl-spinosyn and enhancing the stress resistance of S. pogona, and provides insights into its enhancement on secondary metabolism, which provides a reference for optimizing the production of secondary metabolites in actinomycetes.

Modeling Combination Chelation Regimes To Optimize Cellular Iron Removal and Explore Mechanisms Of Enhanced Chelation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2200-2200
Author(s):  
Evangelia Vlachodimitropoulou ◽  
Garbowski Maciej ◽  
John B Porter
Keyword(s):  
Iron Concentration ◽  
Dual Therapy ◽  
Iron Chelator ◽  
Iron Removal ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Synergy Index ◽  
Cellular Iron ◽  
Low Concentrations ◽  
Oral Chelators

Abstract Introduction Monotherapy with clinically available chelators, namely deferoxaime (DFO), deferasirox (DFX) or deferiprone (DFP) is effective but often slow and suboptimal. Combinations of DFO with DFP have been used clinically to enhance cellular iron mobilization but the conditions under which this occurs have not been studied systematically. With the emergence of DFX, the possibility exists to combine this with either DFO or DFP to enhance chelation. We have developed a system to study the optimal concentrations and times of exposure to these chelators, alone or in combination for maximising cellular iron removal. Isobol modeling has been used to determine whether interaction is additive or synergistic. The demonstration of synergy would imply the primary chelator acting as a ‘sink’ for iron chelated and donated to this sink by low concentrations of a secondary ‘shuttle’ chelator as shown in plasma (Evans et al. TransL. Res, 2010). Methods Human hepatocellular carcinoma (HuH-7) cells were chosen as hepatocytes are the major cell of iron storage in iron overload. Iron concentration was determined using the ferRozine (Riemer et al. Anal Biochem. 2004). A threefold increase of intracellular iron compared to control was obtained by serially treating cells with 10% FBS RPMI media. The cells were then exposed to iron chelator then lysed and intracellular iron concentration determined via the ferrozine assay, normalized against protein content. Cell viability was assessed using 0.4% Trypan blue as well as Acridine Orange /Propidium Iodide and was consistently > 98%. Isobolograms were constructed (Tallarida et al, Pharmacol Ther, 2010) as well as a the synergy index (QUOTE 1-1/R) x 100 (%), where R = difference of areas between the line of additivity and the curve of synergy on the isobologram. This index represents how much of the obtained effect exceeds that expected by additivity of two chelators. Results Monotherapy with DFP, DFX or DFO at clinically relevant concentrations of 1 to 30µM iron binding equivalents (IBE), induced both dose and time dependent cellular iron removal. Dual therapy combinations of all 3 chelators enhanced iron removal at 4, 8 and 12 hours. At 4 hours of incubation, whereas 10µM DFO alone had no demonstrable effect on cellular iron removal, addition of DFP at as little as 1µM IBE increased cellular iron removal. Table 1 shows examples of cellular iron removal at specimen chelator concentrations alone or in combination at 8h. The combination of DFX with DFO, DFX with DFP and DFP with DFO all resulted in enhanced cellular iron removal. The combination of DFP and DFX was the most effective. Isobol plot analysis from multiple chelator concentrations demonstrated synergy for all pairs at 4 and 8 hours of exposure. The derived synergy index at 8h indicates that when DFX and DFO are combined, 49% of the chelation effect is due to synergy in this system and 51% in the case of DFP and DFO combination. Most interestingly, the synergistic effect is even greater, in the case of the two oral chelators DFP and DFX when in combination (59%). Figure 1. Conclusion Remarkably low concentrations of a second chelator are required to enhance cellular iron removal by the primary chelator. Isobol analysis shows synergy rather than additivity as the mechanism for enhanced chelation for all 3 combinations, implying a ‘shuttle’ and ‘sink’ effect. Interestingly, the combination of two oral chelators DFP and DFX showed the most marked enhancement of cellular iron removal, without cellular toxicity, suggesting a potentially powerful therapeutic approach, provided this is also well tolerated clinically. The long plasma half life of once daily oral DFX will allow a continuous ‘sink’ for iron shuttled by the shorter acting DFP. Line of Additivity Curve of Synergy below the line Disclosures: Porter: Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy.

HFE Downregulates Iron Uptake From Transferrin and Induces Iron-Regulatory Protein Activity in Stably Transfected Cells

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3915-3921 ◽  
Author(s):  
H.D. Riedel ◽  
M.U. Muckenthaler ◽  
S.G. Gehrke ◽  
I. Mohr ◽  
K. Brennan ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Regulatory Protein ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Iron Regulatory Proteins ◽  
Cellular Iron

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder of iron metabolism. More than 80% of HH patients are homozygous for a point mutation in a major histocompatibility complex (MHC) class I type protein (HFE), which results in a lack of HFE expression on the cell surface. A previously identified interaction of HFE and the transferrin receptor suggests a possible regulatory role of HFE in cellular iron absorption. Using an HeLa cell line stably transfected with HFE under the control of a tetracycline-sensitive promoter, we investigated the effect of HFE expression on cellular iron uptake. We demonstrate that the overproduction of HFE results in decreased iron uptake from diferric transferrin. Moreover, HFE expression activates the key regulators of intracellular iron homeostasis, the iron-regulatory proteins (IRPs), implying that HFE can affect the intracellular “labile iron pool.” The increase in IRP activity is accompanied by the downregulation of the iron-storage protein, ferritin, and an upregulation of transferrin receptor levels. These findings are discussed in the context of the pathophysiology of HH and a possible role of iron-responsive element (IRE)-containing mRNAs.

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