Skip to main content

Advertisement

SpringerLink
Log in

The expression pattern of ADP-ribosyltransferase 3 in rat traumatic brain injury

  • Original paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

Mammalian ecto ADP-ribosyltransferases (ARTs) can regulate the biological functions of various types of cells by catalyzing the transfer of single ADP-ribose moiety from NAD+ to a specific amino acid in a target protein. ART3 is a member of the known ART family which is involved in cell division, DNA-repair and the regulation of the inflammatory response. To elucidate the expression, cellular localization and possible functions of ART3 in central nervous system (CNS) lesion and repair, we performed an acute traumatic brain injury model in adult rats. Western blot analysis showed that the expression of ART3 in ipsilateral brain cortex increased, then reached a peak at day 3 after traumatic brain injury (TBI), and gradually declined during the following days. But in the contralateral brain cortex, no obvious alterations were observed. Immunohistochemistry revealed the highly significant accumulation of ART3 at the ipsilateral brain in comparison to contralateral cerebral cortex. Double immunofluorescence labeling suggested that ART3 was localized mainly in the plasmalemma of neurons, but not in astrocytes or microglias within 3 mm from the lesion site at day 3 post-injury. In addition, we detected the expression profiles of caspase-3 and growth associated protein 43 (GAP-43) whose changes were correlated with the expression profiles of ART3 in this TBI model. Besides, co-localization of ART3/active caspase-3 and ART3/GAP43 were detected in NeuN-positive cells, respectively. Moreover, Pheochromocytoma (PC12) cells were treated with H2O2 to establish an apoptosis model. The results showed that the expression of ART3 was increased in the concentration and time dependence way. To further examine the involvement of ART3 in apoptosis of PC12, 3-Methoxybenzamide was used in flow cytometry analysis of apoptotic cells stained with Annexin V and PI. The experimental group in which 3-Methoxybenzamide used had a relative low level of apoptotic index compared with the untreated group. Together with previous reports, we hypothesize that ART3 may play important roles in CNS pathophysiology after TBI and further research is needed to have a good understanding of its function and mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ART3:

Mono-ADP-ribosyltransferase 3

CNS:

Central nervous system

TBI:

Traumatic brain injury

SDS:

Sodium dodecyl sulfate

BSA:

Bovine serum albumin

DAB:

Diaminobenzidin

PBS:

Phosphate Buffer solution

NeuN:

Neuronal nuclei

PAGE:

Polyacrylamide gel electrophoresis

GFAP:

Glial fibrillary acidic protein

GAP-43:

Growth associated protein 43

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  • Adriouch S, Ohlrogge W, Haag F, Koch-Nolte F, Seman M (2001) Rapid induction of naive T cell apoptosis by ecto-nicotinamide adenine dinucleotide: requirement for mono(ADP-ribosyl) transferase 2 and a downstream effector. J Immunol 167:196–203

    PubMed  CAS  Google Scholar 

  • Balducci E, Micossi LG, Soldaini E, Rappuoli R (2007) Expression and selective up-regulation of toxin-related mono ADP-ribosyltransferases by pathogen-associated molecular patterns in alveolar epithelial cells. FEBS Lett 581:4199–4204

    Article  PubMed  CAS  Google Scholar 

  • Benowitz LI, Perrone-bizzozero NI (1991) The expression of GAP-43 inrelation to neuronal growth and plascity: when, where, how, and why? Prog Brain Res 89:69–87

    Article  PubMed  CAS  Google Scholar 

  • Braren R, Glowacki G, Nissen M, Haaq F, Koch-Nolte F (1998) Molecular characterization and expression of the gene for mouse NAD + : arginine ecto-mono (ADP-ribosyl) transferase, ART1. Biochem J 336:561–568

    PubMed  CAS  Google Scholar 

  • Bredesen DE (1995) Neural apoptosis. Ann Neurol 38:839–851

    Article  PubMed  CAS  Google Scholar 

  • Christman CW, Salvant JB Jr, Walker SA, Povlishock JT (1997) Characterization of a prolonged regenerative attempt by diffusely injured axons following traumatic brain injury in adult cat: a light and electron microscopic immunocytochemical study. Acta Neuropathol (Berl.) 94:329–337

    Article  CAS  Google Scholar 

  • Clark RS, Kochanek PM, Watkins SC et al (2000) Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem 74:740–753

    Article  PubMed  CAS  Google Scholar 

  • Coggins PJ, McLean K, Zwiers H (1993) Neurogranin, a B-50/GAP-43-immunoreactive C-kinase substrate (BICKS), is ADP-ribosylated. FEBS Lett 335:109–113

    Article  PubMed  CAS  Google Scholar 

  • Corda D, Di Girolamo M (2003) Functional aspects of protein mono-ADP-ribosylation. EMBO J 22:1953–1958

    Article  PubMed  CAS  Google Scholar 

  • Deloulme JC, Janet T, Au D, Storm DR, Sensenbrenner M, Baudier J (1990) Neuromodulin (GAP-43): a neuronal protein kinase C substrate is also present in 0–2A glial cell lineage. Characterization of neuromodulin in secondary cultures of oligodendrocytes and comparison with the neuronal antigen. J Cell Biol 111:1559–1569

    Article  PubMed  CAS  Google Scholar 

  • Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci USA 102:8333–8338

    Article  PubMed  CAS  Google Scholar 

  • Dietrich WD, Chatzipanteli K, Vitarbo E, Wada K, Kinoshita K (2004) The role of inflammatory processes in the pathophysiology and treatment of brain and spinal cord trauma. Acta Neurochir Suppl 89:69–74

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Terwilliger RZ, Nestler EJ (1991) Endogenous ADP-ribosylation in brain: initial characterization of substrate proteins. J Neurochem 57:2124–2132

    Article  PubMed  CAS  Google Scholar 

  • Emery DL, Raghupathi R, Saatman KE, Fischer I, Grady MS, McIntosh TK (2000) Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma. J Comp Neurol 424:521–531

    Article  PubMed  CAS  Google Scholar 

  • Faden AI (2002) Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol 15:707–712

    Article  PubMed  Google Scholar 

  • Felmingham KL, Baguley IJ, Green AM (2004) Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury. Neuropsychology 18:564–571

    Article  PubMed  Google Scholar 

  • Friedrich M, Grahnert A, Klein C, Tschöp K, Engeland K, Hauschildt S (2006a) Genomic organization and expression of the human mono-ADP-ribosyltransferase ART3 gene. Biochim Biophys Acta 1759:270–280

    PubMed  CAS  Google Scholar 

  • Friedrich M, Grahnert A, Paasch U, Tannapfel A, Koch-Nolte F, Hauschildt S (2006b) Expression of toxin-related human mono-ADP-ribosyltransferase 3 in human testes. Asian J Androl 8(3):281–287

    Article  PubMed  CAS  Google Scholar 

  • Grahnert A, Friedrich M, Pfister M, Haag F, Koch-Nolte F, Hauschildt S (2002) Mono-ADP-ribosyltransferases in human monocytes: regulation by lipopolysaccharide. Biochem J 362:717–723

    Article  PubMed  CAS  Google Scholar 

  • Harris NG, Mironova YA, Hovda DA, Sutton RL (2010) Chondroitinase ABC enhances pericontusion axonal sprouting but does not confer robust improvements in behavioral recovery. J Neurotrauma 27:1971–1982

    Article  PubMed  Google Scholar 

  • Heine K, Pust S, Enzenmu¨ller S, Barth H (2008) ADP-Ribosylation of actin by the Clostridium botulinum C2 toxin in mammalian cells results in delayed caspase-dependent apoptotic cell death. Infect Immun 76:4600–4608

    Article  PubMed  CAS  Google Scholar 

  • Hong S, Brass A, Seman M (2009) ART2.1 expression and activity in splenic B cells is modestly up-regulated during incubation in vitro for 24 h, a condition that promotes B cell apoptosis. Purinergic Signal 5:369–383

    Article  PubMed  CAS  Google Scholar 

  • Hulsebosch CE, DeWitt DS, Jenkins LW, Prough D (1998) Traumatic brain injury in rats results in increased expression of Gap-43 that correlates with behavioral recovery. Neurosci Lett 255:83–86

    Article  PubMed  CAS  Google Scholar 

  • Ikonomidou C, Turski L (2002) Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 1:383–386

    Article  PubMed  CAS  Google Scholar 

  • Israelsson C, Bengtsson H, Kylberg A, Kullander K, Lewén A, Hillered L, Ebendal T (2008) Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma 25:959–974

    Article  PubMed  Google Scholar 

  • Keane RW, Kraydieh S, Lotocki G et al (2001a) Apoptotic and antiapoptotic mechanisms after traumatic brain injury. J Cereb Blood Flow Metab 21:1189–1198

    Article  PubMed  CAS  Google Scholar 

  • Keane RW, Kraydieh S, Lotocki G, Alonso OF, Aldana P, Dietrich WD (2001b) Apoptotic and antiapoptotic mechanisms after traumatic brain injury. J Cereb Blood Flow Metab 21:1189–1198

    Article  PubMed  CAS  Google Scholar 

  • Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66:317–326

    Article  PubMed  CAS  Google Scholar 

  • Koch-Nolte F, Haag F, Braren R, Kuhl M, Hoovers J, Balasubramanian S (1997) Two novel human members of an emerging mammalian gene family related to mono-ADP-ribosylating bacterial toxins. Genomics 55:130

    Article  Google Scholar 

  • Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375–378

    Article  PubMed  Google Scholar 

  • Laux T, Fukami K, Thelen M, Golub T, Frey D, Caroni P (2000) GAP43, MARCKS, and CAP23 modulate PI(4,5) P(2) at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism. J Cell Biol 149:1455–1472

    Article  PubMed  CAS  Google Scholar 

  • Leadbeater WE, Gonzalez AM, Logaras N (2006) Intracellular trafficking in neurons and glia of fibroblast growth factor-2, fibroblast growth factor receptor 1 and heparin sulphate proteoglycans in the injured adult rat cerebral cortex. J Neurochem 96:1189–1200

    Article  PubMed  CAS  Google Scholar 

  • Levy I, Wu YQ, Roeckel N, Bulle F, Pawlak A, Siegrist S, Mattei G, Guellaen G (1996) Human testis specifically expresses a homologue of the rodent T lymphocytes RT6 mRNA. FEBS Lett 382:276–280

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Wang Y, Cheng C, Chen Y et al (2010) A relationship between p27(kip1) and Skp2 after adult brain injury: implications for glial proliferation. J Neurotrauma 27:361–371

    Article  PubMed  Google Scholar 

  • Lodhi IJ, Clift RE, Omann GM, Sweeney JF, McMahon KK, Hinshaw DB (2001) Inhibition of mono-ADP-ribosyltransferase activity during the execution phase of apoptosis prevents apoptotic body formation. Arch Biochem Biophys 387:66–77

    Article  PubMed  CAS  Google Scholar 

  • Logan A, Frautschy SA, Gonzalez AM, Baird A (1992) A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci 12:3828–3837

    PubMed  CAS  Google Scholar 

  • Ludden PW (1994) Reversible ADP-ribosylation as a mechanism of enzyme regulation in procaryotes. Mol Cell Biochem 138:123–129

    Article  PubMed  CAS  Google Scholar 

  • Moss J, Vaughan M (1990) ADP-ribosylating Toxins and G proteins: insights into signal transduction. American Society for Microbiology. Science 250:841–842

    Google Scholar 

  • Nortje J, Menon DK (2004) Traumatic brain injury: physiology, mechanisms, and outcome. Curr Opin Neurol 17:711–718

    Article  PubMed  Google Scholar 

  • Rola R, Mizumatsu S, Otsuka S, Morhardt DR, Noble-Haeusslein LJ, Fishman K, Potts MB, Fike JR (2006) Alterations in hippocampal neurogenesis following traumatic brain injury in mice. Exp Neurol 202:189–199

    Article  PubMed  CAS  Google Scholar 

  • Schuman EM, Meffert MK, Schulman H, Madison DV (1994) An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation. Proc Natl Acad Sci USA 91:11958–11962

    Article  PubMed  CAS  Google Scholar 

  • Seman M, Adriouch S, Haag F, Koch-Nolte F (2004a) Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Curr Med Chem 11:857–872

    Article  PubMed  CAS  Google Scholar 

  • Seman M, Adriouch S, Haag F, Koch-Nolte F (2004b) Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Curr Med Chem 11:857–872

    Article  PubMed  CAS  Google Scholar 

  • Teasdale GM, Graham DI (1998) Craniocerebral trauma: protection and retrieval of the neuronal population after injury. Neurosurgery 43:723–737

    Article  PubMed  CAS  Google Scholar 

  • Urrea C, Castellanos DA, Sagen J, Tsoulfas P, Bramlett HM, Dietrich WD (2007) Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat. Restor Neurol Neurosci 25:65–76

    PubMed  CAS  Google Scholar 

  • Wallesch CW, Curio N, Kutz S, Jost S, Bartels C, Synowitz H (2001) Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury. Brain Inj 15:401–412

    Article  PubMed  CAS  Google Scholar 

  • Yu TS, Zhang G, Liebl DJ, Kernie SG (2008) Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. J Neurosci 28:12901–12912

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30870320, No. 31070723, No. 81070275, No. 81171139 and No. 81172879); Natural Science Foundation of Jiangsu province (No. BK2009156, No. BK2009161 and No. BK2010169); Nature Science Foundation of China Ministry of Health (2010-2-025); Key Project Nature Science Foundation of Jiangsu Colleges and Universities (No. 11KJA310002); Nature Science Foundation of Jiangsu Colleges and Universities Grant (09KJB320011); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Wei Shi, Peipei Gong, Yao Hua Yan, Lanchun Ni, Xiaohong Wu, Gang Cui, Xinmin Wu, Xingxing Gu & Jian Chen

  2. Department of Neurosurgery, Affiliated Qidong People Hospital of Nantong University, Nantong, Jiangsu Province, 226200, People’s Republic of China

    Jian Fan

Authors
  1. Wei Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peipei Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yao Hua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lanchun Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaohong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gang Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xinmin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xingxing Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Chen.

Additional information

Wei Shi and Peipei Gong contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, W., Gong, P., Fan, J. et al. The expression pattern of ADP-ribosyltransferase 3 in rat traumatic brain injury. J Mol Hist 43, 37–47 (2012). https://doi.org/10.1007/s10735-011-9366-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-011-9366-y

Keywords

Search

Navigation