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1.
A review on bacterial redox dependent iron transporters and their evolutionary relationship.
Banerjee, S, Chanakira, MN, Hall, J, Kerkan, A, Dasgupta, S, Martin, DW
Journal of inorganic biochemistry. 2022;:111721
Abstract
Iron is an essential yet toxic micronutrient and its transport across biological membranes is tightly regulated in all living organisms. One such iron transporter, the Ftr-type permeases, is found in both eukaryotic and prokaryotic cells. These Ftr-type transporters are required for iron transport, predicted to form α-helical transmembrane structures, and conserve two ArgGluxxGlu (x = any amino acid) motifs. In the yeast Ftr transporter (Ftr1p), a ferroxidase (Fet3p) is required for iron transport in an oxidation coupled transport step. None of the bacterial Ftr-type transporters (EfeU and FetM from E. coli; cFtr from Campylobacter jejuni; FtrC from Brucella, Bordetella, and Burkholderia spp.) contain a ferroxidase protein. Bioinformatics report predicted periplasmic EfeO and FtrB (from the EfeUOB and FtrABCD systems) as novel cupredoxins. The Cu2+ binding and the ferrous oxidation properties of these proteins are uncharacterized and the other two bacterial Ftr-systems are expressed without any ferroxidase/cupredoxin, leading to controversy about the mode of function of these transporters. Here, we review published data on Ftr-type transporters to gain insight into their functional diversity. Based on original bioinformatics data presented here evolutionary relations between these systems are presented.
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2.
Do Extremely Low Gestational Age Neonates Regulate Iron Absorption via Hepcidin?
German, KR, Comstock, BA, Parikh, P, Whittington, D, Mayock, DE, Heagerty, PJ, Bahr, TM, Juul, SE
The Journal of pediatrics. 2022;:62-67.e1
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Abstract
OBJECTIVES To evaluate whether extremely preterm infants regulate iron status via hepcidin. STUDY DESIGN In this retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial, urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo. RESULTS The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio [ZnPP/H]) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-276/7 weeks gestation were analyzed. The median Uhep/UCr concentration was 0.3, 1.3, 0.4, and 0.1 ng/mg at baseline, 2 weeks, 4 weeks, and 12 weeks, respectively, in placebo-treated infants. The median Uhep/UCr value in Epo-treated infants were not significantly different, with the exception of the value at the 2-week time point (median Uhep/UCr, 0.1 ng/mg; P < .001). A significant association was seen between Uhep/UCr and ferritin at 2 weeks (r = 0.63; P < .001) and at 4 weeks (r = 0.41; P = .01) and between Uhep/UCr and ZnPP/H at 2 weeks (r = -0.49; P = .002). CONCLUSIONS Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that extremely preterm neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in extremely preterm neonates, particularly those treated with Epo.
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Experimental study of the remediation of acid mine drainage by Maifan stones combined with SRB.
Guo, X, Hu, Z, Fu, S, Dong, Y, Jiang, G, Li, Y
PloS one. 2022;(1):e0261823
Abstract
The problems of acid mine drainage (AMD) in coal mine acidic wastewaters arise from a range of sources, including severe pollution with heavy metals and SO42- and difficulties during treatment. Based on the ability of Maifan stone to adsorb heavy metals and the dissimilatory reduction of SO42- by sulfate-reducing bacteria (SRB), Maifan stone-sulfate-reducing bacterium-immobilized particles were prepared via immobilization techniques using Shandong Maifan stone as the experimental material. The effects of Maifan stones containing SRB on mitigating AMD were investigated by constructing Dynamic Column 1 with Maifan stone-sulfate-reducing bacterium-immobilized particles and by constructing Dynamic Column 2 with SRB mixed with Maifan stones. By the use of adsorption isotherms, adsorption kinetics, a reduction kinetics model and X-ray diffraction (XRD) and scanning electron microscopy (SEM) studies, the mechanism by which Maifan stone-sulfate-reducing bacterium-immobilized particles mitigate AMD was revealed. The results showed that the total effect of Maifan stone-sulfate-reducing bacterium-immobilized particles on AMD was better than that of biological Maifan stone carriers. The highest rates for the removal of Fe2+, Mn2+, and SO42- in AMD were 90.51%, 85.75% and 93.61%, respectively, and the pH value of the wastewater increased from 4.08 to 7.64. The isotherms for the adsorption of Fe2+ and Mn2+ on Maifan stone-sulfate-reducing bacterium-immobilized particles conformed to the output of the Langmuir model. The adsorption kinetics were in accordance with Lagergren first-order kinetics, and the kinetics for the reduction of SO42- conformed to those of a first-order reaction model.
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Impaired bone marrow microenvironment and stem cells in transfusion-dependent beta-thalassemia.
Zhou, X, Huang, L, Wu, J, Qu, Y, Jiang, H, Zhang, J, Qiu, S, Liao, C, Xu, X, Xia, J, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112548
Abstract
Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.
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Malachite Green, the hazardous materials that can bind to Apo-transferrin and change the iron transfer.
Farhadian, S, Hashemi-Shahraki, F, Amirifar, S, Asadpour, S, Shareghi, B, Heidari, E, Shakerian, B, Rafatifard, M, Firooz, AR
International journal of biological macromolecules. 2022;:790-799
Abstract
Different groups of synthetic dyes might lead to environmental pollution. The binding affinity among hazardous materials with biomolecules necessitates a detailed understanding of their binding properties. Malachite Green might induce a change in the iron transfer by Apo-transferrin. Spectroscopic studies showed malachite green oxalate (MGO) could form the apo-transferrin-MGO complex and change the Accessible Surface Area (ASA) of the key amino acids for iron transfer. According to the ASA results the accessible surface area of Tyrosine, Aspartate, and Histidine of apo-transferrin significantly were changed, which can be considered as a convincing reason for changing the iron transfer. Moreover, based on the fluorescence data MGO could quench the fluorescence intensity of apo-transferrin in a static quenching mechanism. The experimental and Molecular Dynamic simulation results represented that the binding process led to micro environmental changes, around tryptophan residues and altered the tertiary structure of apo-transferrin. The Circular Dichroism (CD) spectra result represented a decrease in the amount of the α-Helix, as well as, increase in the β-sheet volumes of the apo-transferrin structure. Moreover, FTIR spectroscopy results showed a hypochromic shift in the peaks of amide I and II. Molecular docking and MD simulation confirmed all the computational findings.
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Overexpression of ZNT1 and NRAMP4 from the Ni Hyperaccumulator Noccaea caerulescens Population Monte Prinzera in Arabidopsis thaliana Perturbs Fe, Mn, and Ni Accumulation.
Fasani, E, DalCorso, G, Zorzi, G, Agrimonti, C, Fragni, R, Visioli, G, Furini, A
International journal of molecular sciences. 2021;(21)
Abstract
Metalliferous soils are characterized by a high content of metal compounds that can hamper plant growth. The pseudometallophyte Noccaea caerulescens is able to grow on metalliferous substrates by implementing both tolerance and accumulation of usually toxic metal ions. Expression of particular transmembrane transporter proteins (e.g., members of the ZIP and NRAMP families) leads to metal tolerance and accumulation, and its comparison between hyperaccumulator N. caerulescens with non-accumulator relatives Arabidopsis thaliana and Thlaspi arvense has deepened our knowledge on mechanisms adopted by plants to survive in metalliferous soils. In this work, two transporters, ZNT1 and NRAMP4, expressed in a serpentinic population of N. caerulescens identified on the Monte Prinzera (Italy) are considered, and their expression has been induced in yeast and in A. thaliana. In the latter, single transgenic lines were crossed to test the effect of the combined over-expression of the two transporters. An enhanced iron and manganese translocation towards the shoot was induced by overexpression of NcZNT1. The combined overexpression of NcZNT1 and NcNRAMP4 did perturb the metal accumulation in plants.
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Biomimetic poly(γ-glutamic acid) hydrogels based on iron (III) ligand coordination for cartilage tissue engineering.
Wang, P, Zhang, W, Yang, R, Liu, S, Ren, Y, Liu, X, Tan, X, Chi, B
International journal of biological macromolecules. 2021;:1508-1516
Abstract
For the problems in the research on differentiation of mesenchymal stem cells (BMSCs), such as poor differentiation tendency and low differentiation efficiency, a novel photo-crosslinked extracellular matrix (ECM) inspired double network hydrogel that composed of poly(γ-glutamic acid) (γ-PGA) hydrogel and Fe3+ ligand coordination was designed and manufactured. Compared with those traditional γ-PGA based hydrogels, the introduction of Fe3+ significantly enhanced the mechanical properties of the hydrogel and accelerated the chondrogenesis efficiency of BMSCs chondrogenesis. The experimental results confirmed that the mechanical properties of hydrogel enhanced by the introduction of metal ions Fe3+ could promote BMSCs proliferation, induce cartilage-specific gene expression, and increase secretion of hydroxyproline (HYP) and glycosaminoglycan (GAG). As a result, this method could promote chondrogenic differentiation of BMSCs, accelerate the regeneration of cartilage, and was prospective to be conducive to the research work of cartilage defect repair. Thus, the mechanically enhanced γ-PGA hydrogel scaffold by Fe3+ could mediate BMSCs differentiation and provide a scientific and theoretical basis for research and development of biomedical materials on cartilage tissue engineering field.
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8.
Ferroptosis: mechanisms and links with diseases.
Yan, HF, Zou, T, Tuo, QZ, Xu, S, Li, H, Belaidi, AA, Lei, P
Signal transduction and targeted therapy. 2021;(1):49
Abstract
Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.
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GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism.
Rochette, L, Zeller, M, Cottin, Y, Vergely, C
Trends in endocrinology and metabolism: TEM. 2021;(11):875-889
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin (Ang)-converting enzyme 2 (ACE2), which is highly expressed in host cells. The cytokine storm observed in patients with COVID-19 contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasis, and death. Growth and differentiation factor 15 (GDF15), which belongs to the transforming growth factor-β (TGF-β) superfamily of proteins, has a pivotal role in the development and progression of diseases because of its role as a metabolic regulator. In COVID-19, GDF15 activity increases in response to tissue damage. GDF15 appears to be a strong predictor of poor outcomes in patients critically ill with COVID-19 and acts as an 'inflammation-induced central mediator of tissue tolerance' via its metabolic properties. In this review, we examine the potential properties of GDF15 as an emerging modulator of immunity in COVID-19 in association with iron metabolism. The virus life cycle in host cell provides potential targets for drug therapy.
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Broadening horizons: the role of ferroptosis in cancer.
Chen, X, Kang, R, Kroemer, G, Tang, D
Nature reviews. Clinical oncology. 2021;(5):280-296
Abstract
The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy.