DOCSLIB.ORG

Gene Cooption and Convergent Evolution of Oxygen Transport Hemoglobins in Jawed and Jawless Vertebrates

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Cooption and Convergent Evolution of Oxygen Transport Hemoglobins in Jawed and Jawless Vertebrates Gene cooption and convergent evolution of oxygen transport hemoglobins in jawed and jawless vertebrates Federico G. Hoffmanna, Juan C. Opazob, and Jay F. Storza,1 aSchool of Biological Sciences, University of Nebraska, Lincoln, NE 68588; and bInstituto de Ecología y Evolución, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile Edited* by Morris Goodman, Wayne State University, School of Medicine, Detroit, MI, and approved July 6, 2010 (received for review May 14, 2010) Natural selection often promotes evolutionary innovation by coopt- Phylogenetic studies have revealed that vertebrate globins fall ing preexisting genes for new functions, and this process may be into two distinct clades. One clade contains GbX and Ngb, two greatly facilitated by gene duplication. Here we report an example highly divergent genes, which appear to be more closely related of cooptive convergence where paralogous members of the globin to annelid intracellular globins than to any other vertebrate gene superfamily independently evolved a specialized O2 transport globins (20, 21). The other clade contains a set of genes that are function in the two deepest branches of the vertebrate family tree. products of vertebrate-specific duplication events: Cygb, GbE, Specifically, phylogenetic evidence demonstrates that erythroid- GbY, Mb, and the Hbs of jawed vertebrates (gnathostomes) and fi speci cO2 transport hemoglobins evolved independently from dif- jawless fish (cyclostomes, represented by lampreys and hagfish) ferent ancestral precursor proteins in jawed vertebrates (gnathos- (20–22, 28). The monophyly of these vertebrate-specific globins tomes) and jawless fish (cyclostomes, represented by lamprey and is well supported (20, 21), but phylogenetic relationships within hagfish). A comprehensive phylogenetic analysis of the vertebrate this group remain highly uncertain. globin gene superfamily revealed that the erythroid hemoglobins of Because the passive diffusion of O2 in blood plasma is not cyclostomes are orthologous to the cytoglobin protein of gnathos- generally sufficient to meet the metabolic demands of large, tome vertebrates, a hexacoordinate globin that has no O2 transport active animals, the evolution of Hb-mediated blood–O2 trans- function and that is predominantly expressed in fibroblasts and port represented a key physiological innovation in vertebrate life related cell types. The phylogeny reconstruction also revealed that that opened up new opportunities for the evolution of aerobic vertebrate-specific globins are grouped into four main clades: (i) metabolism. In gnathostomes, Hb is a tetrameric protein as- cyclostome hemoglobin + cytoglobin, (ii) myoglobin + globin E, sembled from two α-chain and two β-chain subunits. The pro- (iii) globin Y, and (iv)theα- and β-chain hemoglobins of gnathos- genitors of the α- and β-globin gene families arose via tandem tomes. In the hemoglobins of gnathostomes and cyclostomes, multi- duplication of an ancestral, single-copy globin gene approxi- subunit quaternary structures provide the basis for cooperative O2 mately 450–500 mya, after the gnathostome common ancestor binding and allosteric regulation by coupling the effects of ligand diverged from jawless fishes (29–31). In the α2β2 Hb tetramers of binding at individual subunits with interactions between subunits. most extant gnathostomes, the cooperativity of O2 binding stems However, differences in numerous structural details belie their in- from an oxygenation-linked transition in quaternary structure. dependent origins. This example of convergent evolution of protein The origin of cooperativity was preceded by the gene duplication function provides an impressive demonstration of the ability of nat- that gave rise to structurally distinct α- and β-chain subunits (11, ural selection to cobble together complex design solutions by tin- 30, 32). By contrast, in the Hbs of extant cyclostomes, coopera- kering with different variations of the same basic protein scaffold. tivity of O2 binding stems from oxygenation-linked dissociation of multimers into ligated monomers (33–39). For this reason, cytoglobin | gene family evolution | globin | hagfish | lamprey cyclostome Hbs have been considered “... a transition stage between invertebrate and vertebrate hemoglobins” (40). Phylo- atural selection often promotes evolutionary innovation by genetic studies of vertebrate globins have presented tree topol- Ncoopting preexisting genes for new functions. Gene coop- ogies that are not consistent with a single origin of O2 transport tion may have played a role in major episodes of adaptive change Hbs (22, 28, 41). However, incomplete sampling of taxa and gene in multicellular organisms, and it appears to be an important lineages has not permitted any definitive conclusions. mechanism for generating morphological and physiological di- Here we report a comprehensive phylogenetic reconstruction versity (1–5). Gene duplication may be an especially important of the vertebrate globin gene superfamily that includes repre- facilitator of cooptive evolution (6). This is well illustrated in the sentatives from each of the major lineages of gnathostomes as vertebrate globin gene superfamily, because there are several well as cyclostomes. Results of this analysis revealed that the well-documented cases where paralogous gene copies have ac- erythroid Hbs of cyclostomes and gnathostomes are not orthol- quired distinct physiological functions and/or patterns of ex- ogous proteins. Instead, the functionally similar O2 transport pression (7–11). proteins were coopted from phylogenetically distinct and an- Globins are ancient proteins that are present in each of the ciently diverged globin protein precursors. This represents an three domains of life (11–13). Throughout the 20th century, myo- example of “cooptive convergence,” where paralogous members globin (Mb; an O2 storage protein in muscle) and hemoglobin (Hb; of the same gene family independently evolve the same spe- an O2 transport protein in red blood cells) were the only known globin proteins in vertebrates (8, 14). Early in the 21st century, comparative genomic studies revealed a surprising diversity of Author contributions: F.G.H., J.C.O., and J.F.S. designed research; performed research; novel globin genes in vertebrates, including neuroglobin (Ngb) analyzed data; and wrote the paper. (15), cytoglobin (Cygb) (16–18), globin-E (GbE) (19), globin-X The authors declare no conflict of interest. (GbX) (20), and globin-Y (GbY) (21). The discovery of these novel *This Direct Submission article had a prearranged editor. globin genes has motivated experimental studies to elucidate their 1To whom correspondence should be addressed. E-mail: [email protected]. physiological functions and evolutionary studies to assess their This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. phylogenetic affinities and taxonomic distributions (22–28). 1073/pnas.1006756107/-/DCSupplemental. 14274–14279 | PNAS | August 10, 2010 | vol. 107 | no. 32 www.pnas.org/cgi/doi/10.1073/pnas.1006756107 Downloaded by guest on September 23, 2021 cialization of function in different lineages. After being pressed Bayesian posterior probability of 1.00 (Fig. 1). Cyclostome Hbs, into service as O2 transport proteins, the two paralogous globins Cygb, GbE, GbYs, and Mb were all placed in strongly supported independently evolved similar biochemical properties in extant monophyletic groups, with maximum likelihood bootstrap support cyclostomes and gnathostomes. values that ranged from 96% to 100% and Bayesian posterior The Hbs of cyclostome and gnathostome vertebrates are en- probabilities ≥0.99. Our phylogeny reconstructions also grouped capsulated in red blood cells and both proteins provide a highly the vertebrate-specific globins into four distinct clades: (i)cyclo- α efficient means of O2 transport from the respiratory surfaces to stome Hb + Cygb, (ii) Mb + GbE, (iii)GbY,and(iv)the -and the cells of metabolizing tissues while also contributing to the β-chain Hbs of gnathostomes (this latter clade is sister to the other fi transport of CO2 back to the gas exchange organs. The efficiency three clades of vertebrate-speci c globins) (Fig. 1). of both Hbs as O2 transport proteins stems from subunit–subunit We performed a comprehensive sensitivity analysis to evaluate interactions (homotropic effects), which account for the coop- how the phylogenetic results were affected by the use of different erativity of O2 binding, and the deoxygenation-linked binding of alignment algorithms, the use of different amino acid substi- allosteric ligands (heterotropic effects), which provides a mech- tution models, and the use of different outgroup sequences (e.g., anism for the cellular regulation of Hb–O2 affinity. In the Hbs of vertebrate GbX or globins from basal chordates such as the sea cyclostomes and gnathostomes, cooperativity and allosteric regula- squirt, Ciona intestinalis). To do this, we performed phylogenetic tion are made possible by oxygenation-linked changes in quaternary searches for 10 alternative alignments of our sequences under structure (42). Thus, the O2 transport Hbs of both taxa convergently three different models of amino acid substitution. In each of evolved distinct forms of both homotropic and heterotropic co- these different analyses, vertebrate globins consistently fell into operative effects from different ancestral protein monomers that the four main clades described above, and cyclostome Hb was lacked cooperativity. invariably
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]
  • Using Information in Taxonomists' Heads to Resolve Hagfish And
    This article was downloaded by: [Max Planck Inst fuer Evolutionsbiologie] On: 03 September 2013, At: 07:01 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Historical Biology: An International Journal of Paleobiology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ghbi20 Using information in taxonomists’ heads to resolve hagfish and lamprey relationships and recapitulate craniate–vertebrate phylogenetic history Maria Abou Chakra a , Brian Keith Hall b & Johnny Ricky Stone a b c d a Department of Biology , McMaster University , Hamilton , Canada b Department of Biology , Dalhousie University , Halifax , Canada c Origins Institute, McMaster University , Hamilton , Canada d SHARCNet, McMaster University , Hamilton , Canada Published online: 02 Sep 2013. To cite this article: Historical Biology (2013): Using information in taxonomists’ heads to resolve hagfish and lamprey relationships and recapitulate craniate–vertebrate phylogenetic history, Historical Biology: An International Journal of Paleobiology To link to this article: http://dx.doi.org/10.1080/08912963.2013.825792 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information.
    [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]
  • 300556969.Pdf
    ARTICLE https://doi.org/10.1038/s42003-019-0713-y OPEN The vertebrate Aqp14 water channel is a neuropeptide-regulated polytransporter François Chauvigné1, Ozlem Yilmaz2, Alba Ferré1, Per Gunnar Fjelldal3, Roderick Nigel Finn 1,2*& Joan Cerdà 1* 1234567890():,; Water channels (aquaporins) were originally discovered in mammals with fourteen sub- families now identified (AQP0-13). Here we show that a functional Aqp14 subfamily phy- logenetically related to AQP4-type channels exists in all vertebrate lineages except hagfishes and eutherian mammals. In contrast to the water-selective classical aquaporins, which have four aromatic-arginine constriction residues, Aqp14 proteins present five non-aromatic constriction residues and facilitate the permeation of water, urea, ammonia, H2O2 and gly- cerol. Immunocytochemical assays suggest that Aqp14 channels play important osmor- egulatory roles in piscine seawater adaptation. Our data indicate that Aqp14 intracellular trafficking is tightly regulated by the vasotocinergic/isotocinergic neuropeptide and receptor systems, whereby protein kinase C and A transduction pathways phosphorylate highly conserved C-terminal residues to control channel plasma membrane insertion. The neuro- peptide regulation of Aqp14 channels thus predates the vasotocin/vasopressin regulation of AQP2-5-6 orthologs observed in tetrapods. These findings demonstrate that vertebrate Aqp14 channels represent an ancient subfamily of neuropeptide-regulated polytransporters. 1 IRTA-Institute of Biotechnology and Biomedicine (IBB), Universitat
    [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]