DOCSLIB.ORG

Neuroglobin, Cytoglobin, and Myoglobin Contribute to Hypoxia Adaptation of the Subterranean Mole Rat Spalax

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neuroglobin, Cytoglobin, and Myoglobin Contribute to Hypoxia Adaptation of the Subterranean Mole Rat Spalax Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax Aaron Avivia,1,2, Frank Gerlachb,1, Alma Joela, Stefan Reussc, Thorsten Burmesterd, Eviatar Nevoa,2, and Thomas Hankelnb,2 aInstitute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel; bInstitute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany; cInstitute of Microanatomy and Neurobiology, School of Medicine, Johannes Gutenberg-University Mainz, D-55131 Mainz, Germany; and dZoological Institute and Museum, Biocenter Grindel, University of Hamburg, D-20146 Hamburg, Germany Contributed by Eviatar Nevo, November 1, 2010 (sent for review July 2, 2010) The subterranean mole rat Spalax is an excellent model for studying with the hypoxia-sensitive rodent Rattus norvegicus, Spalax survives adaptation of a mammal toward chronic environmental hypoxia. substantially longer at low ambient O2 levels and high CO2 without Neuroglobin (Ngb) and cytoglobin (Cygb) are O2-binding respiratory serious deleterious effects or behavioral changes (6). proteins and thus candidates for being involved in molecular hyp- Hypoxia tolerance mechanisms identified in Spalax as com- oxia adaptations of Spalax. Ngb is expressed primarily in vertebrate pared with R. norvegicus include blood properties, anatomical nerves, whereas Cygb is found in extracellular matrix-producing and biochemical changes in respiratory organs (2, 4), and dif- cells and in some neurons. The physiological functions of both pro- ferences in the structure and function of a growing list of gene products (7–10). Transcription patterns of genes related to hyp- teins are not fully understood but discussed with regard to O2 sup- fi ply, the detoxification of reactive oxygen or nitrogen species, and oxic stress differ interspeci cally in Spalax (5, 11) and between Spalax and rat, involving key players such as erythropoietin (Epo) apoptosis protection. Spalax Ngb and Cygb coding sequences are and its receptors, and hypoxia-inducible factor-1α (Hif-1α) (12, strongly conserved. However, mRNA and protein levels of Ngb in 13). An important adaptation of Spalax to hypoxic habitats is Spalax brain are 3-fold higher than in Rattus norvegicus under nor- mediated by an increased blood vessel density, which is triggered EVOLUTION moxia. Importantly, Spalax expresses Ngb in neurons and addition- by a constitutively higher expression (compared with rat) of vas- ally in glia, whereas in hypoxia-sensitive rodents Ngb expression is cular endothelial growth factor (Vegf), Hif-1α, and HuR, a post- limited to neurons. Hypoxia causes an approximately 2-fold down- transcriptional stabilizer of Vegf mRNA (6, 14). regulation of Ngb mRNA in brain of rat and mole rat. A parallel The aerobic metabolism of mammals relies on respiratory regulatory response was found for myoglobin (Mb) in Spalax and proteins that function in the delivery and storage of O2.Hbin rat muscle, suggesting similar functions of Mb and Ngb. Cygb also erythrocytes transports O2 from the lungs to inner organs (15). revealed an augmented normoxic expression in Spalax vs. rat brain, Myoglobin (Mb) in cardiac and striated muscles acts as a local O2 fi but not in heart or liver, indicating distinct tissue-speci c functions. store and facilitates intracellular diffusion of O2 (16). Ten years Hypoxia induced Cygb transcription in heart and liver of both mam- ago, neuroglobin (Ngb) and cytoglobin (Cygb) were discovered mals, with the most prominent mRNA up-regulation (12-fold) in Spalax as unique members of the mammalian globin family (17). The heart. Our data suggest that tissue globins contribute to the re- physiological functions of Ngb and Cygb are still uncertain. In markable tolerance of Spalax toward environmental hypoxia. This most mammals, Ngb resides in neurons of the central and pe- is consistent with the proposed cytoprotective effect of Ngb and ripheral nervous systems, as well as in endocrine organs (18, 19). Cygb under pathological hypoxic/ischemic conditions in mammals. Ngb may have an Mb-like role in supplying O2 to the mitochon- drial respiratory chain (18, 20, 21). Alternatively, it may function as a scavenger of reactive oxygen or nitrogen species (ROS/RNS) xygen levels that are inadequate to sustain cellular energy (22, 23) or protect cells from cytochrome c-induced apoptosis (24, Oproduction constitute a life-threatening condition for mam- 25). Regardless of its ultimate role, there is conclusive evidence mals. Metabolically most active tissues (e.g., nerve cells) are ex- that Ngb localization is tightly linked to active oxidative metab- quisitely sensitive to a reduction of O2 (hypoxia), and humans are olism and mitochondria (19, 20). The highest Ngb level was found severely affected by hypoxic disease conditions like stroke or myo- in the neuronal retina, which also has the highest O -consuming fi 2 cardial ischemia. It is therefore mandatory to investigate the speci c rate in the body (20, 26). Several studies have shown that Ngb is adaptations evolved by mammals that live in naturally hypoxic cyto- and neuroprotective (27–29). Recently it was demonstrated environments where low ambient O2 tensions limit the availability that in the hooded seal, a diving mammal that tolerates prolonged of O2 to the organism (1). hypoxia of the brain (30), Ngb is expressed in astrocytes (31). This The blind mole rat Spalax spends its entire life in underground may indicate an unusual shift of oxidative metabolism from neu- burrows that can be extremely hypoxic/hypercapnic (2, 3). The rons to glial cells. Spalacidae, originating 25–40 million years ago, have evolved Cygb occurs predominantly in the fibroblast cell lineage, as physiological strategies enabling their respiratory and cardiovas- well as in some neurons (32–34). The function of Cygb is even cular systems to cope with hypoxia more efficiently than other less clear than that of Ngb but has been interpreted in terms of mammalian species (2, 4). The four karyotypically distinct allo- ROS defense or O2 supply to certain enzymes (17, 33, 35). species of Spalax in Israel are adapted to different climatic regimes. The strongest differences in ecological conditions are observed between Spalax galili (karyotype 2n = 52), inhabiting the northern Author contributions: A.A., F.G., and T.H. designed research; A.A., F.G., A.J., S.R., and T.B. cool-humid Upper Galilee Mountains with heavy soil, which often performed research; F.G. analyzed data; and A.A., S.R., T.B., E.N., and T.H. wrote the becomes flooded, and Spalax judaei (2n = 60), which reside in the paper. warm-dry south with light-aerated soil. The most efficient hypoxic The authors declare no conflict of interest. adaptation has consequently been demonstrated in S. galili,with 1A.A. and F.G. contributed equally to this work. higher normoxic breathing and heart rate as well as higher he- 2To whom correspondence may be addressed. E-mail: [email protected], matocrit and Hb levels as compared with S. judaei (2, 5). Another [email protected], or [email protected]. two Spalax species, Spalax golani (2n = 54) and Spalax carmeli This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. (2n = 58), are intermediate in their hypoxia adaptation. Compared 1073/pnas.1015379107/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1015379107 PNAS Early Edition | 1of6 Downloaded by guest on September 24, 2021 Globins are candidates that may enable Spalax to better survive low ambient oxygen conditions. To understand the particular role of Ngb, Cygb, and Mb in hypoxia tolerance, we have studied their sequences, expression patterns, and gene regulation in different Spalax species in comparison with rat. The data provide indirect evidence to the physiological function(s) of Ngb and Cygb in mam- mals and point to the biomedical significance of these proteins. Results Sequence Analysis of Spalax Ngb, Cygb, and Mb. Ngb and Cygb gene sequences from S. carmeli were reported previously (36). Here we have cloned, sequenced, and compared the coding regions of Ngb and Cygb from all four Spalax species (Fig. S1). As in other mam- mals (18, 37), the Spalax Ngb cDNA encodes a strongly conserved protein of 151 amino acids. The four Spalax species maximally differ by two amino acids, and the best match to other genera was found with mouse Ngb (94% identity, 96% similarity). Spalax Cygb cDNAs encode a protein of 190 amino acids, as typical for most other mammals. Cygb proteins of S. carmeli and S. galili are iden- tical and show two amino acid differences to S. golani and S. judaei, which has one additional substitution. S. golani Cygb is 95% iden- tical/99% similar to mouse Cygb. Only very few Spalax-specific amino acid replacements were observed for Ngb and Cygb (Fig. S1). Homology modeling showed that these substitutions are on the surface of the Ngb and Cygb proteins (Fig. S2). Except for the minor differences, Spalax Ngb and Cygb include the conserved sequence hallmarks of functional O2 carriers [e.g., the proximal and distal His (F8 and E7) and PheCD1, which are involved in heme and ligand binding]. The coding region of Spalax Mb (462 bp) translates into a protein of 154 amino acids. Its sequence—here obtained from S. carmeli (2n = 58)—matched the published S. judaei Mb pro- Fig. 1. Ngb immunofluorescence in Spalax brain. (A) Frontal section of tein sequence (38) with 98.1% identity. Again, all functional Spalax brain at the level of the lateral ventricle (LV) and anterior commissure positions are conserved, and the observed replacements are (ac). Ngb staining of neurons was found in the piriform (Pir), insular, sensory, found in other mammals as well. and motor regions of the cerebral cortex (CC) and in the striatum (caudate nucleus-putamen, CPu), as well as medial and basal forebrain regions. fi Expression Patterns of Ngb and Cygb in Spalax Tissue.
Load more

Recommended publications
  • Extracellular Neuroglobin As a Stress-Induced Factor Activating
    cancers Article Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer 1, , 1, 2 1 Marco Fiocchetti * y, Virginia Solar Fernandez y, Marco Segatto , Stefano Leone , Paolo Cercola 3, Annalisa Massari 3, Francesco Cavaliere 3 and Maria Marino 1,* 1 Department of Science, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy; [email protected] (V.S.F.); [email protected] (S.L.) 2 Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, 86090 Pesche (IS), Italy; [email protected] 3 Division of Senology, Belcolle Hospital, Str. Sammartinese, 01100 Viterbo, Italy; [email protected] (P.C.); [email protected] (A.M.); [email protected] (F.C.) * Correspondence: marco.fi[email protected] (M.F.); [email protected] (M.M.); Tel.: +39-06-5733-6455 (M.F.); +39-06-5733-6320 (M.M.); Fax: +39-06-5733-6321 (M.F. & M.M.) These authors contributed equally to this work. y Received: 27 July 2020; Accepted: 26 August 2020; Published: 29 August 2020 Abstract: Components of tumor microenvironment, including tumor and/or stromal cells-derived factors, exert a critical role in breast cancer (BC) progression. Here we evaluated the possible role of neuroglobin (NGB), a monomeric globin that acts as a compensatory protein against oxidative and apoptotic processes, as part of BC microenvironment. The extracellular NGB levels were evaluated by immunofluorescence of BC tissue sections and by Western blot of the culture media of BC cell lines.
    [Show full text]
  • Biochemical and Cellular Studies of Vertebrate Globins
    Biochemical and Cellular Studies of Vertebrate Globins By Shun Wilford Tse Thesis submitted for the degree of Doctor of Philosophy School of Biological Sciences University of East Anglia September 2015 © This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and that no quotations from the thesis, nor any information derived there-from may be published without the author's prior, written consent. Abstract Human cytoglobin is a small heme-containing protein in the globin superfamily with a wide range of tissue and organ distribution. Although several cellular functions have been proposed for cytoglobin, the exact physiological function is still not fully defined. Recently, cytoglobin has been implicated to have a regulatory role in cancer cells to control cell proliferation and migration depending on cellular oxygen level. In order to gain a better understanding of a structure-to-function relationship of cytoglobin as a heme-protein and to evaluate its possible physiological function(s) in cancer cells, a combination of techniques, including protein engineering and advanced spectroscopies, was deployed. In this study, recombinant human cytoglobin purified from E.coli was purified as a monomeric protein, but displayed a dimeric property in solution. An intra-molecular disulphide bond is formed within the protein which has a redox potential at ca -280 mV. Advanced spectroscopic studies confirmed a low-spin bis-histidyl heme in cytoglobin in both ferric and ferrous state regardless of the state of the disulphide bond. Furthermore, nitrite reductase activitiy in globins was investigated in detail using myoglobin as a model to explore the biochemical basis of the distal histidine residue in determining activity.
    [Show full text]
  • Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes
    International Journal of Molecular Sciences Review The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes Anna Bilska-Wilkosz *, Małgorzata Iciek, Magdalena Górny and Danuta Kowalczyk-Pachel Chair of Medical Biochemistry, Jagiellonian University Collegium Medicum ,7 Kopernika Street, Kraków 31-034, Poland; [email protected] (M.I.); [email protected] (M.G.); [email protected] (D.K.-P.) * Correspondence: [email protected]; Tel.: +48-12-4227-400; Fax: +48-12-4223-272 Received: 5 May 2017; Accepted: 16 June 2017; Published: 20 June 2017 Abstract: Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide oxidation pathway. In this review, we discuss the current state of knowledge on the interactions between hydrogen sulfide and hemoglobin, myoglobin and neuroglobin and postulate that thiosulfate is a metabolically important product of this processes. Hydrogen sulfide oxidation by ferric hemoglobin, myoglobin and neuroglobin has been defined as a non-canonical hydrogen sulfide oxidation pathway. Until recently, it appeared that the goal of thiosulfate production was to delay irreversible oxidation of hydrogen sulfide to sulfate excreted in urine; while thiosulfate itself was only an intermediate, transient metabolite on the hydrogen sulfide oxidation pathway. In the light of data presented in this paper, it seems that thiosulfate is a molecule that plays a prominent role in the human body. Thus, we hope that all these findings will encourage further studies on the role of hemoproteins in the formation of this undoubtedly fascinating molecule and on the mechanisms responsible for its biological activity in the human body.
    [Show full text]
  • Supporting Information
    Supporting Information Biagioli et al. 10.1073/pnas.0813216106 SI Text and the procedure was repeated twice. Single cells were then RNA Isolation, Reverse Transcription, qPCR, Cloning, and Sequencing. resuspended in panning buffer and incubated on lectin-coated RNA was extracted from cell lines and blood by using TRIzol panning plates for 15 min at room temperature. Nonadherent reagent (Invitrogen) and following vendor instructions. cells were transferred to the next panning plate (four pannings, RNA was extracted from LCM- or FACS-purified cells with an 15 min each). Then, nonadherent cells were collected, centri- Absolutely RNA Nanoprep Kit (Stratagene). Single-strand fuged, and resuspended in serum-free neuronal medium or PBS. cDNA was obtained from purified RNA by using the iSCRIPT A similar procedure was also followed for the dissociation of cDNA Synhesis Kit (Bio-Rad) according to the manufacturer’s cortical and hippocampal astrocytes and oligodendrocytes. instructions. Quantitative RT-PCR was performed by using A cell strainer with 70-␮m nylon mesh was used to obtain a SYBER-Green PCR Master Mix and an iQ5 Real-Time PCR single-cell suspension (BD Falcon) before sorting. 7-AAD Detection System (Bio-Rad). (Beckman–Coulter) was added to the cell suspension to exclude Quantitative RT-PCR was performed with an iCycler IQ dead cells. A high-speed cell sorter (MoFlo) was used to sort (Bio-Rad); ␤-actin was used as an endogenous control to nor- subpopulation of cells expressing GFP. Sorting parameters used malize the expression level of target genes. Primers were chosen for the three different populations are visualized in Fig.
    [Show full text]
  • Adult, Embryonic and Fetal Hemoglobin Are Expressed in Human Glioblastoma Cells
    514 INTERNATIONAL JOURNAL OF ONCOLOGY 44: 514-520, 2014 Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells MARWAN EMARA1,2, A. ROBERT TURNER1 and JOAN ALLALUNIS-TURNER1 1Department of Oncology, University of Alberta and Alberta Health Services, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada; 2Center for Aging and Associated Diseases, Zewail City of Science and Technology, Cairo, Egypt Received September 7, 2013; Accepted October 7, 2013 DOI: 10.3892/ijo.2013.2186 Abstract. Hemoglobin is a hemoprotein, produced mainly in Introduction erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell Globins are hemo-containing proteins, have the ability to types including human and rodent neurons of embryonic bind gaseous ligands [oxygen (O2), nitric oxide (NO) and and adult brain, but not astrocytes and oligodendrocytes. carbon monoxide (CO)] reversibly. They have been described Human glioblastoma multiforme (GBM) is the most aggres- in prokaryotes, fungi, plants and animals with an enormous sive tumor among gliomas. However, despite extensive basic diversity of structure and function (1). To date, hemoglobin, and clinical research studies on GBM cells, little is known myoglobin, neuroglobin (Ngb) and cytoglobin (Cygb) repre- about glial defence mechanisms that allow these cells to sent the vertebrate globin family with distinct function and survive and resist various types of treatment. We have tissue distributions (2). During ontogeny, developing erythro- shown previously that the newest members of vertebrate blasts sequentially express embryonic {[Gower 1 (ζ2ε2), globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are Gower 2 (α2ε2), and Portland 1 (ζ2γ2)] to fetal [Hb F(α2γ2)] expressed in human GBM cells.
    [Show full text]
  • Neuroglobin and Cytoglobin Fresh Blood for the Vertebrate Globin Family
    EMBO reports Neuroglobin and cytoglobin Fresh blood for the vertebrate globin family Alessandra Pesce, Martino Bolognesi+, Alessio Bocedi1, Paolo Ascenzi1, Sylvia Dewilde2, Luc Moens2, Thomas Hankeln3 & Thorsten Burmester4 Department of Physics–INFM and Center for Excellence in Biomedical Research, University of Genova, Via Dodecaneso 33, I-16146 Genova, 1Department of Biology, University ‘Roma Tre’, Viale Guglielmo Marconi 446, I-00146 Roma, Italy, 2Department of Biochemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium, 3Institute of Molecular Genetics, Johannes Gutenberg University of Mainz, Becherweg 32, D-55099 Mainz and 4Institute of Zoology, Johannes Gutenberg University of Mainz, Müllerweg 6, D-55099 Mainz, Germany Received August 7, 2002; revised October 8, 2002; accepted October 18, 2002 Neuroglobin and cytoglobin are two recently discovered (Wittenberg, 1970, 1992; Antonini and Brunori, 1971; Perutz, members of the vertebrate globin family. Both are intracellular 1979, 1990; Dickerson and Geis, 1983; Bunn and Forget, 1986; proteins endowed with hexacoordinated heme-Fe atoms, in Brunori, 1999; Weber and Vinogradov, 2001; Merx et al., 2002), their ferrous and ferric forms, and display O2 affinities comparable although they can also carry out enzymatic functions (Minning with that of myoglobin. Neuroglobin, which is predominantly et al., 1999; Ascenzi et al., 2001). expressed in nerve cells, is thought to protect neurons from Four types of globin, differing in structure, tissue distribution hypoxic–ischemic injury. It is of ancient evolutionary origin, and likely in function, have been discovered in man and other and is homologous to nerve globins of invertebrates. vertebrates: hemoglobin, myoglobin, neuroglobin and cyto- Cytoglobin is expressed in many different tissues, although at globin.
    [Show full text]
  • A Gene-Environment Study of Cytoglobin in the Human and Rat Hippocampus
    A Gene-Environment Study of Cytoglobin in the Human and Rat Hippocampus Christian Ansgar Hundahl1,3, Betina Elfving2, Heidi Kaastrup Mu¨ ller2, Anders Hay-Schmidt3, Gregers Wegener2,4* 1 Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia, 2 Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, 3 Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark, 4 Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa Abstract Background: Cytoglobin (Cygb) was discovered a decade ago as the fourth vertebrate heme-globin. The function of Cygb is still unknown, but accumulating evidence from in vitro studies point to a putative role in scavenging of reactive oxygen species and nitric oxide metabolism and in vivo studies have shown Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (nNOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression. Methods: Immunohistochemistry was used to compare Cygb expression in the human and rat hippocampi as well as Cygb and nNOS co-expression in the rat hippocampus. Transcription and translation of Cygb and nNOS were investigated using quantitative real-time polymerase chain reaction (real-time qPCR) and Western blotting on hippocampi from Flinders (FSL/ FRL) rats exposed to CRS. Principal Findings: Cygb expression pattern in the human and rat hippocampus was found to be similar.
    [Show full text]
  • Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation
    Molecular Neurobiology (2019) 56:2101–2122 https://doi.org/10.1007/s12035-018-1212-8 Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation Zoë P. Van Acker1 & Evi Luyckx1 & Sylvia Dewilde1 Received: 22 November 2017 /Accepted: 26 June 2018 /Published online: 10 July 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract After its discovery in 2000, the notion grew that neuroglobin, a neuronal specific heme protein, is involved in cytoprotection. To date, neuroglobin levels have been positively correlated with a beneficial outcome in a plethora of neurotoxic insults, e.g., ischemic and traumatic brain injuries and Alzheimer’s disease. The first part of this review goes further into these changes of neuroglobin expression upon different neuronal insults as well as the underlying regulation. In the second part, we shed light on the mechanisms by which neuroglobin contributes to neuroprotection, being (i) the scavenging and detoxification of reactive oxygen/nitrogen species, (ii) the augmentation of the threshold for apoptosis initiation, (iii) its contribution to an anti-inflammatory milieu, and (iv) tissue regeneration. We also consider different neuroglobin models to address as yet unanswered questions. Based on the recent findings and progress in the field, we invigorate the avenues of neuroglobin in neurological ailments to increase in the coming years. Keywords Neuroglobin . Expression . Neuroprotection . Apoptosis . Inflammation . Neurogenesis Introduction system [4, 5]. Highest expression levels are detected in the mammalian hypothalamus, which shows 100-fold higher tran- Sustainment of homeostasis in the central nervous system scription rates than other key Ngb expression regions as the is essential to support vital physiological functions.
    [Show full text]
  • Apoptotic Cells Inflammasome Activity During the Uptake of Macrophage
    Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021 is online at: average * The Journal of Immunology , 26 of which you can access for free at: 2012; 188:5682-5693; Prepublished online 20 from submission to initial decision 4 weeks from acceptance to publication April 2012; doi: 10.4049/jimmunol.1103760 http://www.jimmunol.org/content/188/11/5682 Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells Marie E. Benoit, Elizabeth V. Clarke, Pedro Morgado, Deborah A. Fraser and Andrea J. Tenner J Immunol cites 56 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription http://www.jimmunol.org/content/suppl/2012/04/20/jimmunol.110376 0.DC1 This article http://www.jimmunol.org/content/188/11/5682.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 29, 2021. The Journal of Immunology Complement Protein C1q Directs Macrophage Polarization and Limits Inflammasome Activity during the Uptake of Apoptotic Cells Marie E.
    [Show full text]
  • The Expression Profile of Cytoglobin in Human
    THE EXPRESSION PROFILE OF CYTOGLOBIN IN HUMAN FIBROTIC LUNG, AND THE PROTECTIVE ROLE OF CYTOGLOBIN IN HYPOXIA AND OXIDATIVE STRESS IN VITRO. By MELINDA CARPENTER A thesis submitted to the The University of Birmingham for the degree of DOCTOR OF PHILOSOPHY School of Bioscience University of Birmingham September 2009 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract Cytoglobin (CYGB), a novel member of the globin family, has been shown to be upregulated in response to hypoxia, oxidative stress and fibrogenesis. Presented here is evidence of CYGB expression within cells of fibrotic lesions taken from patients with Idiopathic Pulmonary Fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD). CYGB staining was observed in fibroblasts, endothelial cells, type II pneumocytes, type I pneumocytes, haematopoietic stem cells and inflammatory cells, which were identified using cell specific markers. Cell types which express other members of the globin family, including smooth muscle and red blood cells were negative for CYGB. Fibroblasts were consistently positive for CYGB. CYGB expression was consistently positive within the lesion, and more variable at the edge. This study also provides evidence of an increase in CYGB expression in response to hypoxic and oxidative stress in vitro; however there was no evidence of cytoprotection with over expression of CYGB in response to these insults.
    [Show full text]
  • Additional File 3.Pdf
    ************ globins ************ >Pdu_Egb_A1a MNGITVFLILAMASASLADDCTQLDMIKVKHQWAEVYGVESNRQEFGLAVFKRFFVIHPD RSLFVNVHGDNVYSPEFQAHVARVLAGVDILISSMDQEAIFKAAQKHYADFHKSKFGEVPLVEFGTAMRDVLP KYVGLRNYDNDSWSRCYAYITSKVE >Pdu_Egb_A1b MKGLLVFLVLASVSASLASECSSLDKIKVKNQWA RIHGSPSNRKAFGTAVFKRFFEDHPDRSLFANVNGNDIYSADFQAHVQRVFGGLDILIVSLDQDDLFTAAKSH YSEFHKKLGDVPFAEFGVAFLDTLSDFLPLRDYNQDPWSRCYNYIIS >Pdu_Egb_A1c MNTVTVVLVLLG CIASAMTGDCNTLQRTKVKYQWSIVYGATDNRQAFGTLVWRDFFGLYPDRSLFSGVRGENIYSPEFRAHVVRV FAGFDILISLLDQEDILNSALAHYAAFHKQFPSIPFKEFGVVLLEALAKTIPEQFDQDAWSQCYAVIVAGVTA >Pdu_Egb_A1d_alpha MYQILSVAVLVLSCLALGTLGEEVCGPLERIKVQHQWVSVYGADHDRLKVSTL VWKDFFEHHPEERARFERVNSDNIFSGDFRAHMVRVFAGFDLLIGVLNEEEIFKSAMIHYTKMHNDLGVTTEI IKEFGKSIARVLPEFMDGKPDITAWRPCFNLIAAGVSE >Pdu_Egb_A1d_beta MYFSYFTAAASYLSVAVLVLSCLVQGILGEEVCGPLEKIKVQHQWASAYRGDHD RLKMSTLVWKDFFAHNPEERARFERVHSDDIYSGDFRAHMVRVFAGFDLLIGALNQEDIFRSAMIHYTKMHKK LGVTYEIGIEFGKSIGRVLPEFIDGKLDITAWRPCYKLIATGVDE >Pdu_Egb_A1d_gamma MYLSVAVLVLSCLALGTQGEEVCGPLEKIKVQHQWASAYRGDHDRLKMSTLVW KDFFAHHPEERARFERVHSDDIYSGDFRAHMVRVFAGFDLLIGVLNQDEIFKSAMIHYTKMHNDLGVKTEIVL EFGKSIARVLPDFIDGKPDITAWRPCFKLIAAGVSE >Pdu_Egb_A2 MNNLVILVGLLCLGLTSATKCGPL QRLKVKQQWAKAYGVGHERLELGIALWKSIFAQDPESRSIFTRVHGDDVRHPAFEAHIARVFNGFDRIISSLT DEDVLQAQLAHLKAQHIKLGISAHHFKLMRTGLSYVLPAQLGRCFDKEAWGSCWDEVIYPGIKSL >Pdu_Egb_B1 MLVLAVFVAALGLAAADQCCSIEDRNEVQALWQSIWSAENTGKRTIIGHQIFEELFDINP GTKDLFKRVNVEDTSSPEFEAHVLRVMNGLDTLIGVLDDPATGYSLITHLAEQHKAREGFKPSYFKDIGVALK RVLPQVASCFNPEAWDHCFNGFVEAITNKMNAL >Pdu_Egb_B2 MLVLVLSLAFLGSALAEDCCSAADRKTVLRDWQSVWSAEFTGRRVAIGTAIFEELFAIDA GAKDVFKNVAVDKPESAEWAAHVIRVINGLDLAINLLEDPRALKEELLHLAKQHRERDGVKAVYFDEIGRALL
    [Show full text]
  • Strand Breaks for P53 Exon 6 and 8 Among Different Time Course of Folate Depletion Or Repletion in the Rectosigmoid Mucosa
    SUPPLEMENTAL FIGURE COLON p53 EXONIC STRAND BREAKS DURING FOLATE DEPLETION-REPLETION INTERVENTION Supplemental Figure Legend Strand breaks for p53 exon 6 and 8 among different time course of folate depletion or repletion in the rectosigmoid mucosa. The input of DNA was controlled by GAPDH. The data is shown as ΔCt after normalized to GAPDH. The higher ΔCt the more strand breaks. The P value is shown in the figure. SUPPLEMENT S1 Genes that were significantly UPREGULATED after folate intervention (by unadjusted paired t-test), list is sorted by P value Gene Symbol Nucleotide P VALUE Description OLFM4 NM_006418 0.0000 Homo sapiens differentially expressed in hematopoietic lineages (GW112) mRNA. FMR1NB NM_152578 0.0000 Homo sapiens hypothetical protein FLJ25736 (FLJ25736) mRNA. IFI6 NM_002038 0.0001 Homo sapiens interferon alpha-inducible protein (clone IFI-6-16) (G1P3) transcript variant 1 mRNA. Homo sapiens UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 15 GALNTL5 NM_145292 0.0001 (GALNT15) mRNA. STIM2 NM_020860 0.0001 Homo sapiens stromal interaction molecule 2 (STIM2) mRNA. ZNF645 NM_152577 0.0002 Homo sapiens hypothetical protein FLJ25735 (FLJ25735) mRNA. ATP12A NM_001676 0.0002 Homo sapiens ATPase H+/K+ transporting nongastric alpha polypeptide (ATP12A) mRNA. U1SNRNPBP NM_007020 0.0003 Homo sapiens U1-snRNP binding protein homolog (U1SNRNPBP) transcript variant 1 mRNA. RNF125 NM_017831 0.0004 Homo sapiens ring finger protein 125 (RNF125) mRNA. FMNL1 NM_005892 0.0004 Homo sapiens formin-like (FMNL) mRNA. ISG15 NM_005101 0.0005 Homo sapiens interferon alpha-inducible protein (clone IFI-15K) (G1P2) mRNA. SLC6A14 NM_007231 0.0005 Homo sapiens solute carrier family 6 (neurotransmitter transporter) member 14 (SLC6A14) mRNA.
    [Show full text]