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Heme iron

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https://www.readbyqxmd.com/read/29242190/the-rv2633c-protein-of-mycobacterium-tuberculosis-is-a-non-heme-di-iron-catalase-with-a-possible-role-in-defenses-against-oxidative-stress
#1
Zhongxin Ma, Kyle T Strickland, Michelle D Cherne, Esha Sehanobish, Kyle H Rohde, William T Self, Victor L Davidson
The Rv2633c gene in Mycobacterium tuberculosis is rapidly upregulated after macrophage infection, suggesting that Rv2633c is involved in M. tuberculosis pathogenesis. However, the activity and role of the Rv2633c protein in host colonization is unknown. Here, we analyzed the Rv2633c protein sequence, which revealed the presence of an HHE cation-binding domain common in hemerythrin-like proteins. Phylogenetic analysis indicated that Rv2633c is a member of a distinct subset of hemerythrin-like proteins exclusive to mycobacteria...
December 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29236734/freeze-dried-lactobacillus-plantarum-299v-increases-iron-absorption-in-young-females-double-isotope-sequential-single-blind-studies-in-menstruating-women
#2
Michael Hoppe, Gunilla Önning, Lena Hulthén
BACKGROUND: The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption. OBJECTIVE: The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843)...
2017: PloS One
https://www.readbyqxmd.com/read/29228768/recovery-of-mrs3%C3%AE-mrs4%C3%AE-saccharomyces-cerevisiae-cells-under-iron-sufficient-conditions-and-the-role-of-fe580
#3
Michael J Moore, Joshua Wofford, Andrew Dancis, Paul Alan Lindahl
Mrs3 and Mrs4 are mitochondrial inner membrane proteins that deliver an unidentified cytosolic iron species into the matrix for use in iron-sulfur-cluster (ISC) and heme biosynthesis. The Mrs3/4 double-deletion strain (ΔΔ) grew slowly in iron-deficient glycerol/ethanol medium but recovered to WT rates in iron-sufficient medium. ΔΔ cells grown under both iron-deficient and iron-sufficient respiring conditions accumulated large amounts of iron relative to WT cells, indicating iron homeostatic dysregulation regardless of nutrient iron status...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29227633/a-distal-loop-controls-product-release-chemo-and-regio-selectivity-in-cytochrome-p450-decarboxylases
#4
Jose A Amaya, Cooper D Rutland, Nic Leschinsky, Thomas M Makris
The cytochrome P450 OleT utilizes hydrogen peroxide (H2O2) to catalyze the decarboxylation or hydroxylation of fatty acid (FA) substrates. Both reactions are initiated through the abstraction of a substrate hydrogen atom by the high-valent iron-oxo intermediate known as Compound I. Here, we specifically probe the influence of substrate coordination on OleT reaction partitioning through the combined use of fluorescent and EPR-active FA probes, and mutagenesis of a structurally disordered F-G loop that is distal from the heme-iron active-site...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29222267/new-therapeutic-targets-in-transfusion-dependent-and-independent-thalassemia
#5
REVIEW
M Domenica Cappellini, Irene Motta
β-Thalassemias are characterized by reduced production of β-globin chain, resulting in α/β-chain unbalance and precipitation of α-globin-heme complexes and determining ineffective erythropoiesis. Ineffective erythropoiesis, chronic hemolytic anemia, and compensatory hematopoietic expansion are the disease hallmarks, and they are related to the severity of the chain unbalance. Several clinical forms of β-thalassemia, including the coinheritance of β-thalassemia with hemoglobin E resulting in hemoglobin E/β-thalassemia, have been described...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218050/heme-drives-oxidative-stress-associated-cell-death-in-human-neutrophils-infected-with-leishmania-infantum
#6
Graziele Quintela-Carvalho, Nívea F Luz, Fabiana S Celes, Dalila L Zanette, Daniela Andrade, Diego Menezes, Natália M Tavares, Claudia I Brodskyn, Deboraci B Prates, Marilda S Gonçalves, Camila I de Oliveira, Roque P Almeida, Marcelo T Bozza, Bruno B Andrade, Valeria M Borges
Free heme is an inflammatory molecule capable of inducing migration and activation of neutrophils. Here, we examine the heme-driven oxidative stress-associated cell death mechanisms in human neutrophils infected with Leishmania infantum, an etiologic agent of visceral leishmaniasis (VL). We first performed exploratory analyses in a population of well characterized treatment-naïve VL patients as well as uninfected controls, who were part of previously reported studies. We noted a positive correlation between serum concentrations of heme with heme oxygenase-1 (HO-1) and lactate deydrogenase, as well as, a negative correlation between heme values and peripheral blood neutrophils counts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212619/zinc-protoporphyrin-to-heme-ratio-and-ferritin-as-measures-of-iron-sufficiency-in-the-neonatal-intensive-care-unit
#7
Kendell German, Phuong T Vu, Kimberly N Grelli, Christopher Denton, Gina Lee, Sandra E Juul
OBJECTIVES: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios as biomarkers of iron status in neonates, determine how specific clinical events affected these measures, and assess how iron status changed during hospitalization. STUDY DESIGN: We performed a retrospective study of all infants with paired ferritin and ZnPP/H measurements between October 2014 and May 2016. Concordance of these measurements, effects of sepsis, red blood cell transfusion, erythropoietin treatment, and iron supplementation were assessed...
December 4, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29212341/scavenging-reactive-oxygen-species-production-normalizes-ferroportin-expression-and-ameliorates-cellular-and-systemic-iron-disbalances-in-hemolytic-mouse-model
#8
Naveen Kumar Tangudu, Betuel Alan, Francesca Vinchi, Katharina Woerle, Dilay Lai, Sabine Vettorazzi, Kerstin Leopold, Maja Vujic Spasic
AIMS: The release of large amounts of free heme into the circulation, overproduction of reactive oxygen species (ROS) and the activation of toll-like receptor (Tlr)-4 dependent responses are considered critical for the ability of heme to promote oxidative stress and to initiate pro-inflammatory responses, posing a serious threat to the body. A deep understanding of the consequences of heme overload on the regulation of cellular and systemic iron homeostasis is however, still lacking. RESULTS: The effects of heme on iron metabolism were studied in primary macrophages and in mouse models of acute and chronic hemolysis...
December 6, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29211462/the-eponymous-cofactors-in-cytochrome-p460s-from-ammonia-oxidizing-bacteria-are-iron-porphyrinoids-whose-macrocycles-are-dibasic
#9
Meghan A Smith, Kyle M Lancaster
The enzymes hydroxylamine oxidoreductase and cytochrome (cyt) P460 contain related unconventional "heme P460" cofactors. These cofactors are unusual in their inclusion of nonstandard cross-links between amino acid side chains and the heme macrocycle. Mutagenesis studies performed on the Nitrosomonas europaea cyt P460 that remove its lysine-heme cross-link show that the cross-link is key to defining the spectroscopic properties and kinetic competence of the enzyme. However, exactly how this cross-link confers these features remains unclear...
December 6, 2017: Biochemistry
https://www.readbyqxmd.com/read/29208364/dopamine-promotes-cellular-iron-accumulation-and-oxidative-stress-responses-in-macrophages
#10
Stefanie Dichtl, David Haschka, Manfred Nairz, Markus Seifert, Chiara Volani, Oliver Lutz, Günter Weiss
Iron is essential for many biological functions including neurotransmitter synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts tyrosine to dopamine and further to norepinephrine. As the shared chemical structure, called catechol, may potentially bind iron we questioned whether tyrosine derived hormones would impact on cellular iron homeostasis in macrophages, which are central for the maintenance of body iron homeostasis. Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect of catecholamines and found that only dopamine but neither tyrosine, nor norepinephrine, affected cellular iron homeostasis...
December 2, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29203959/cancer-cell-specific-mitochondrial-reactive-oxygen-species-promote-non-heme-iron-uptake-and-enhance-the-proliferation-of-gastric-epithelial-cancer-cell
#11
Hiromu Ito, Hiromi Kurokawa, Aki Hirayama, Hiroko P Indo, Hideyuki J Majima, Hirofumi Matsui
Iron is an essential nutrient for life and is involved in many important processes such as oxygen transport and DNA synthesis. However, excess amounts of iron can cause carcinogenesis by producing reactive oxygen species. Thus, the cellular transport of iron must be tightly regulated. In the human body, iron may be present as heme or non-heme iron. The mechanisms governing the cellular transport of these forms have not been clearly elucidated. We previously reported that the expression of an important heme transporter, heme carrier protein 1 was regulated by cancer-specific reactive oxygen species derived from mitochondria...
November 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/29199426/characterization-of-key-factors-of-anchovy-engraulis-japonicus-meat-in-the-nanoparticle-mediated-enhancement-of-non-heme-iron-absorption
#12
Yaqun Zou, Liang Zhao, Guangxin Feng, Yu Miao, Haohao Wu, Ming-Yong Zeng
Anchovy (Engraulis japonicus) meat (AM) has been shown to promote non-heme iron absorption via a ferric oxyhydroxide nanoparticle (FeONP)-mediated mechanism. Here, formulation modifications of an egg-white-based AIN-93G diet with AM fractions resulted hemoglobin regeneration efficiencies in anemic rats following an order control (23.69 ± 3.99%) < ferrous-sulfate-replacement of ferric citrate (39.89 ± 2.97%) ≈ de-haemed-AM-protein-replacement of egg white (45.88 ± 4.76%) ≈ AM-lipid-replacement of soybean oil (43...
December 4, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29195491/ros-mediated-heme-degradation-and-cytotoxicity-induced-by-iron-nanoparticles-hemoglobin-and-lymphocyte-cells-as-targets
#13
Sepideh Mirzaei, Zari Hadadi, Farnoosh Attar, Seyyedeh Elaheh Mousavi, Seyed Shahaboddin Zargar, Aida Tajik, Ali Akbar Saboury, Seyed Mahdi Rezayat, Mojtaba Falahati
Nanoparticles (NPs) due to their small size and high surface area induce remarkable adverse effects on the biological systems. However, the exact mechanism by which NPs interacted with biological system and induce their adverse effects is still an enigma. Herein, the interaction of zero valent iron NPs (ZVFe NPs) with human hemoglobin (Hb) was evaluated using a variety of techniques including circular dichroism (CD), fluorescence, and UV-visible (UV-vis) spectroscopy methods. Also, the cytotoxicity of ZVFe NPs on the human lymphocyte cell line as a model of blood system cell line was investigated by reactive oxygen species (ROS), caspase-9 and caspase-3 activities assays...
December 1, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29193867/improved-safety-margin-for-embryotoxicity-in-rats-for-the-new-endoperoxide-artefenomel-oz439-as-compared-to-artesunate
#14
Robert L Clark, Tammye L Edwards, Monica Longo, Joseph Kinney, Don K Walker, Jon Rhodes, Sally A Clode, Thomas Rückle, Timothy Wells, Nicole Andenmatten, Anna Christine Huber
BACKGROUND: Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety. METHODS: As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos...
November 28, 2017: Birth Defects Research
https://www.readbyqxmd.com/read/29192767/a-trojan-horse-for-light-triggered-bifurcated-production-of-singlet-oxygen-and-fenton-reactive-iron-within-cancer-cells
#15
Daniela Cioloboc, Christopher Kennedy, Emily N Boice, Emily R Clark, Donald M Kurtz
Traditional photodynamic therapy for cancer relies on dye-photosensitized generation of singlet oxygen. However, therapeutically effective singlet oxygen generation requires well-oxygenated tissues, whereas many tumor environments tend to be hypoxic. We describe a platform for targeted enhancement of photodynamic therapy that produces singlet oxygen in oxygenated environments and hydroxyl radical, which is typically regarded as the most toxic reactive oxygen species, in hypoxic environments. The 24-subunit iron storage protein bacterioferritin (Bfr) has the unique property of binding 12 heme groups in its protein shell...
December 1, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29186806/the-silencing-of-carotenoid-%C3%AE-hydroxylases-by-rna-interference-in-different-maize-genetic-backgrounds-increases-the-%C3%AE-carotene-content-of-the-endosperm
#16
(no author information available yet)
Maize (Zea mays L.) is a staple food in many parts of Africa, but the endosperm generally contains low levels of the pro-vitamin A carotenoid β-carotene, leading to vitamin A deficiency disease in populations relying on cereal-based diets. However, maize endosperm does accumulate high levels of other carotenoids, including zeaxanthin, which is derived from β-carotene via two hydroxylation reactions. Blocking these reactions could therefore improve the endosperm β-carotene content. Accordingly, we used RNA interference (RNAi) to silence the endogenous ZmBCH1 and ZmBCH2 genes, which encode two non-heme di-iron carotenoid β-hydroxylases...
November 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29183661/design-synthesis-and-evaluation-against-mycobacterium-tuberculosis-of-azole-piperazine-derivatives-as-dicyclotyrosine-cyy-mimics
#17
Hend A A Abd El-Wahab, Mauro Accietto, Leonardo B Marino, Kirsty J McLean, Colin W Levy, Hamdy M Abdel-Rahman, Mahmoud A El-Gendy, Andrew W Munro, Ahmed S Aboraia, Claire Simons
Three series of azole piperazine derivatives that mimic dicyclotyrosine (cYY), the natural substrate of the essential Mycobacterium tuberculosis cytochrome P450 CYP121A1, were prepared and evaluated for binding affinity and inhibitory activity (MIC) against M. tuberculosis. Series A replaces one phenol group of cYY with a C3-imidazole moiety, series B includes a keto group on the hydrocarbon chain preceding the series A imidazole, whilst series C explores replacing the keto group of the piperidone ring of cYY with a CH2-imidazole or CH2-triazole moiety to enhance binding interaction with the heme of CYP121A1...
November 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29182862/on-the-inhibition-of-mammalian-15-lipoxygenase-by-three-ebselen-like-drugs-a-qm-mm-and-mm-pbsa-comparative-study
#18
Anna Cebrián-Prats, Tiffani Rovira, Patricia Saura, Àngels González-Lafont, José M Lluch
Ebselen is a potent competitive inhibitor of the active form of rabbit 15-lipoxygenase, an enzyme involved in many inflammatory diseases. Light induced Z-to-E isomerization of the ebselen-like 2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester (BODTCM) molecule was used to convert the weak (Z)-BOTDCM inhibitor into the (E)-isomer with much higher inhibitory capacity. In this study, the binding modes of ebselen, (E)-BOTDCM and (Z)-BOTDCM have been analyzed to provide molecular insights on the inhibitory potency of ebselen and on the geometric-isomer specificity of (E)- and (Z)-BOTDCM inhibitors...
November 28, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29180398/inhibition-of-heme-oxygenase-ameliorates-anemia-and-reduces-iron-overload-in-%C3%AE-thalassemia-mouse-model
#19
Daniel Garcia-Santos, Amel Hamdi, Zuzana Saxova, Carine Fillebeen, Kostas Pantopoulos, Monika Horvathova, Prem Ponka
Thalassemias are a heterogeneous group of red blood cell disorders, considered as major cause of morbidity and mortality among genetic diseases. However, there is still no universally available cure for thalassemias. The underlying basis of thalassemia pathology is the premature apoptotic destruction of erythroblasts causing ineffective erythropoiesis. In β-thalassemia, β-globin synthesis is reduced causing α-globin accumulation. Unpaired globin chains, with heme attached to them, accumulate in thalassemic erythroblasts causing oxidative stress and the premature cell death...
November 27, 2017: Blood
https://www.readbyqxmd.com/read/29180047/iron-status-and-oxidative-stress-in-the-aged-rabbit-heart
#20
Domenico Lapenna, Giuliano Ciofani, Sante Donato Pierdomenico, Maria Adele Giamberardino, Ettore Porreca
Altered iron status may be relevant to the pathophysiology of aging. We have assessed redox-active catalytic low molecular weight iron (LMWI), non-heme iron (NHI), heme iron (HI), and total iron (TI) in the aerobically perfused hearts of aged rabbits (AR, about 4.5years old) and young adult control rabbits (YACR, 3-4months old); myocardial lipid and protein oxidation were also assessed as oxidative stress biomarkers. The levels of LMWI and NHI, as well as of lipid and protein oxidation, were higher, while HI content was lower, in the hearts of AR than in those of YACR; TI did not differ significantly between the two groups...
November 24, 2017: Journal of Molecular and Cellular Cardiology
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