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Heme iron

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https://www.readbyqxmd.com/read/28213526/structural-and-mechanistic-insights-into-hemoglobin-catalyzed-hydrogen-sulfide-oxidation-and-the-fate-of-polysulfide-products
#1
Victor Vitvitsky, Pramod K Yadav, Sojin An, Javier Seravalli, Uhn-Soo Cho, Ruma Banerjee
Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize H2S but lacking organelles, cannot dispose off H2S via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes H2S to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low-spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213091/convergence-of-hepcidin-deficiency-systemic-iron-overloading-heme-accumulation-and-rev-erb%C3%AE-%C3%AE-activation-in-aryl-hydrocarbon-receptor-elicited-hepatotoxicity
#2
Kelly A Fader, Rance Nault, Mathew P Kirby, Gena Markous, Jason Matthews, Timothy R Zacharewski
Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01-30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28206992/heme-oxygenase-1-promoter-polymorphisms-do-they-modulate-neonatal-hyperbilirubinemia
#3
M Kaplan, R J Wong, D K Stevenson
The role of genetic factors in the modulation of serum bilirubin levels and the pathophysiology of neonatal hyperbilirubinemia is being increasingly recognized. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme by which heme is catabolized to biliverdin and thence to bilirubin, with the simultaneous release of equimolar quantities of ferrous iron (Fe(3+)) and carbon monoxide. Polymorphisms of the HO-1 gene promoter may modulate transcriptional activity, thereby augmenting or attenuating HO-1 expression with resultant modulation of the production of bilirubin...
February 16, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28205448/association-between-red-meat-consumption-and-colon-cancer-a-systematic-review-of-experimental-results
#4
Nancy D Turner, Shannon K Lloyd
A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28203649/increased-iron-export-by-ferroportin-induces-restriction-of-hiv-1-infection-in-sickle-cell-disease
#5
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Adv
https://www.readbyqxmd.com/read/28202542/m%C3%A3-ssbauer-spectra-of-mouse-hearts-reveal-age-dependent-changes-in-mitochondrial-and-ferritin-iron-levels
#6
Joshua D Wofford, Mrinmoy Chakrabarti, Paul Alan Lindahl
Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from (57)Fe-enriched mice were evaluated by Mossbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood while the other was due to [Fe4S4](2+) clusters and Fe(II) hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196881/engineered-holocytochrome-c-synthases-that-biosynthesize-new-cytochromes-c
#7
Deanna L Mendez, Shalon E Babbitt, Jeremy D King, John D'Alessandro, Michael B Watson, Robert E Blankenship, Liviu M Mirica, Robert G Kranz
Cytochrome c (cyt c), required for electron transport in mitochondria, possesses a covalently attached heme cofactor. Attachment is catalyzed by holocytochrome c synthase (HCCS), leading to two thioether bonds between heme and a conserved CXXCH motif of cyt c In cyt c, histidine (His19) of CXXCH acts as an axial ligand to heme iron and upon release of holocytochrome c from HCCS, folding leads to formation of a second axial interaction with methionine (Met81). We previously discovered mutations in human HCCS that facilitate increased biosynthesis of cyt c in recombinant Escherichia coli Focusing on HCCS E159A, novel cyt c variants in quantities that are sufficient for biophysical analysis are biosynthesized...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193844/heme-assimilation-in-schizosaccharomyces-pombe-requires-cell-surface-anchored-protein-shu1-and-vacuolar-transporter-abc3
#8
Thierry Mourer, Vincent Normant, Simon Labbe
The Schizosaccharomyces pombe shu1(+) gene encodes a cell-surface protein required for assimilation of exogenous heme. In this study, shaving experiments showed that Shu1 is released from membrane preparations when spheroplast lysates are incubated with phosphoinositide-specific phospholipase C (PI-PLC). Shu1 cleavability by PI-PLC and its predicted hydropathy profile strongly suggested that Shu1 is a glycosylphosphatidyl inositol-anchored protein. When heme biosynthesis is selectively blocked in hem1Δ mutant cells, the heme analog zinc mesoporphyrin IX (ZnMP) first accumulates into vacuoles and then subsequently, within the cytoplasm in a rapid and Shu1-dependent manner...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186648/the-recipient-s-heme-oxygenase-1-promoter-region-polymorphism-is-associated-with-cardiac-allograft-vasculopathy
#9
Kathrin Freystaetter, Martin Andreas, Martin Bilban, Thomas Perkmann, Alexandra Kaider, Marco Masetti, Alfred Kocher, Michael Wolzt, Andreas Zuckermann
BACKGROUND: Heme oxygenase-1 (HO-1) catalyses the degradation of heme to biliverdin, free iron and carbon monoxide. The promoter region contains a highly polymorphic (GT)n repeat, where shorter (GT)n repeat sequences are linked to higher transcriptional activity, which was shown to correlate with a cytoprotective effect. Higher HO-1 levels may protect from cardiac allograft vasculopathy. METHODS: Cardiac allograft recipients transplanted between 1988 and 2012 were analysed for the HO-1 (GT)n repeat polymorphism using PCR and DNA fragment analysis with capillary electrophoresis...
February 10, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28185024/disturbed-iron-metabolism-in-erythropoietic-protoporphyria-and-association-of-gdf15-and-gender-with-disease-severity
#10
Jasmin Barman-Aksoezen, Domenico Girelli, Caterina Aurizi, Xiaoye Schneider-Yin, Natascia Campostrini, Luca Barbieri, Elisabeth I Minder, Gianfranco Biolcati
Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. In addition to photosensitivity, patients frequently exhibit low serum iron and a microcytic hypochromic anemia. The aims of this study were to (1) search for factors related to PPIX concentration in EPP, and (2) characterize anemia in EPP, i...
February 9, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28184354/gallium-protoporphyrin-ix-inhibits-pseudomonas-aeruginosa-growth-by-targeting-cytochromes
#11
Sarah Hijazi, Paolo Visca, Emanuela Frangipani
Pseudomonas aeruginosa is a challenging pathogen due to both innate and acquired resistance to antibiotics. It is capable of causing a variety of infections, including chronic lung infection in cystic fibrosis (CF) patients. Given the importance of iron in bacterial physiology and pathogenicity, iron-uptake and metabolism have become attractive targets for the development of new antibacterial compounds. P. aeruginosa can acquire iron from a variety of sources to fulfill its nutritional requirements both in the environment and in the infected host...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28181998/zinc-protoporphyrin-heme-ratio-as-parameter-of-iron-status-in-moderately-preterm-infants-natural-course-and-associations-in-the-first-4-months
#12
C G de Waal, L Uijterschout, M Abbink, B Boersma, P Vos, W W Rövekamp, F Hudig, M D Akkermans, J B van Goudoever, F Brus
OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation...
February 9, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28174304/the-pyruvate-and-%C3%AE-ketoglutarate-dehydrogenase-complexes-of-pseudomonas-aeruginosa-catalyze-pyocyanin-and-phenazine-1-carboxylic-acid-reduction-via-the-subunit-dihydrolipoamide-dehydrogenase
#13
Nathaniel R Glasser, Benjamin X Wang, Julie A Hoy, Dianne K Newman
Phenazines are a class of redox-active molecules produced by diverse bacteria and archaea. Many of the biological functions of phenazines, such as mediating signaling, iron acquisition, and redox homeostasis, derive from their redox activity. While prior studies have focused on extracellular phenazine oxidation by oxygen and iron, here we report a search for reductants and catalysts of intracellular phenazine reduction in Pseudomonas aeruginosa Enzymatic assays in cell-free lysate, together with crude fractionation and chemical inhibition, indicate that P...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28170277/simulation-of-the-bottleneck-controlling-access-into-a-rieske-active-site-predicting-substrates-of-naphthalene-1-2-dioxygenase
#14
Diego Ernesto Escalante, Kelly Gardner Aukema, Lawrence P Wackett, Alptekin Aksan
Naphthalene 1,2-dioxygenase has been computationally understudied despite the extensive experimental knowledge obtained for this enzyme, including numerous crystal structures and over 100 demonstrated substrates. In this study, we have developed a substrate prediction model that moves away from the traditional active site-centric approach to include the energetics of substrate entry into the active site. By comparison with experimental data, the accuracy of the model for predicting substrate oxidation is 92%, with a positive predictive value of 93% and a negative predictive value of 98%...
February 7, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28169355/enhancement-of-5-aminolevulinic-acid-based-fluorescence-detection-of-side-population-defined-glioma-stem-cells-by-iron-chelation
#15
Wenqian Wang, Kouichi Tabu, Yuichiro Hagiya, Yuta Sugiyama, Yasuhiro Kokubu, Yoshitaka Murota, Shun-Ichiro Ogura, Tetsuya Taga
Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167947/the-heme-connection-linking-erythrocytes-and-macrophage-biology
#16
REVIEW
Md Zahidul Alam, Samir Devalaraja, Malay Haldar
Erythroid function and development is intimately linked to macrophages. The primary function of erythrocytes is oxygen delivery, which is mediated by iron-containing hemoglobin. The major source of this iron is a recycling pathway where macrophages scavenge old and damaged erythrocytes to release iron contained within the heme moiety. Macrophages also promote erythropoiesis by providing a supportive niche in the bone marrow as an integral component of "erythorblastic islands." Importantly, inflammation leads to alterations in iron handling by macrophages with significant impact on iron homeostasis and erythropoiesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28167288/impact-of-tet2-deficiency-on-iron-metabolism-in-erythroblasts
#17
Kyoko Inokura, Tohru Fujiwara, Kei Saito, Tatsuya Iino, Shunsuke Hatta, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Kenichi Ishizawa, Kazuya Shimoda, Hideo Harigae
Sideroblastic anemia is characterized by the presence of ring sideroblasts, which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both acquired and congenital forms of sideroblastic anemia. However, the mechanism leading to ring sideroblast formation remains elusive. Acquired sideroblastic anemia is usually observed in myelodysplastic syndrome. Because a subset of myelodysplastic syndrome harbors a somatic mutation of TET2, it may be involved in iron metabolism and/or heme biosynthesis in erythroblasts...
February 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28165393/reduced-sharpin-and-lubac-formation-may-contribute-to-ccl%C3%A2-or-acetaminophen-induced-liver-cirrhosis-in-mice
#18
Takeshi Yamamotoya, Yusuke Nakatsu, Yasuka Matsunaga, Toshiaki Fukushima, Hiroki Yamazaki, Sunao Kaneko, Midori Fujishiro, Takako Kikuchi, Akifumi Kushiyama, Fuminori Tokunaga, Tomoichiro Asano, Hideyuki Sakoda
Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28163077/regulation-of-trace-elements-and-redox-status-in-striatum-of-adult-rats-by-long-term-aerobic-exercise-depends-on-iron-uptakes
#19
Hua-Bo Wu, De-Sheng Xiao
We investigated the effects of aerobic exercise (AE) on trace element contents and redox status in the striatum of rats with different diet iron. Weaned female rats were randomly fed with iron-adequate diet (IAD), iron-deficient diet (IDD), and iron-overloaded diet (IOD). After feeding their respective diet for 1 month, the rats fed with same diet were divided into swimming and maintaining sedentary (S) group. After 3 months, the non-heme iron (NHI), Mn, Cu, and Zn in the striatum were measured. Meanwhile, malonaldehyde acid (MDA), total superoxide dismutase activity, hydroxyl radical scavenging activity, and total antioxidant capacity were also analyzed...
February 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28161963/effects-of-heme-degradation-products-on-reactivation-of-latent-hiv-1
#20
P Shankaran, M Madlenakova, V Hajkova, D Jilich, I Svobodova, A Horinek, Y Fujikura, Z Melkova
Human immunodeficiency virus (HIV-1) infection can be currently controlled by combined antiretroviral therapy, but a sterilizing cure is not achievable as this therapy does not target persistent HIV-1 in latent reservoirs. Therefore, different latency reversal agents are intensively explored in various models. We have previously observed that heme arginate, a drug approved for human use, reveals a strong synergism with PKC inducers in reactivation of the latent provirus. Heme is physiologically decomposed by heme oxygenases into 3 degradation products: iron (Fe2+), carbon monoxide (CO) and biliverdin which is further converted to bilirubin by biliverdin reductase...
February 6, 2017: Acta Virologica
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