Skip to main content
SpringerLink
Log in

Poly-ADP-Ribosylation of Vascular Endothelial Growth Factor and Its Implications on Angiogenesis

  • Conference paper
  • First Online:
Biochemical Roles of Eukaryotic Cell Surface Macromolecules

Part of the book series: Advances in Experimental Medicine and Biology ((volume 749))

Abstract

Vascular Endothelial Growth Factor, an endothelial cell specific growth factor, is a glycoprotein that exerts its effect through cell surface receptor dependent signaling events. Apart from glycosylation, a key posttranslational modification of VEGF involves polyADP ribosylation. While glycosylation is critical in its secretion, PAR modification is not critical for its secretion as evidenced by absence of any significant effect of 3-aminobenzamide, an inhibitor of PAR modification on the level of VEGF secreted into the medium by cells in culture. However, the PAR modification appeared to be critical in its angiogenic potential as evidenced by a reciprocal relation between the level of PAR modification and the angiogenic effect of VEGF in CAM assay.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adamis AP, Yeo KT et al (1994) Increased vascular endothelial growth factor in the vitreous of eyes with proliferative diabetic retinopathy. Am J Opthalmol 118:445–450

    CAS  Google Scholar 

  • Aiello LP, King G et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  PubMed  CAS  Google Scholar 

  • Baldwin ME, Roufail S, Halford MM et al (2001) Multiple forms of mouse vascular endothelial growth factor D are generated by RNA splicing and proteolysis. J Biol Chem 276:44307–44314

    Article  PubMed  CAS  Google Scholar 

  • Barleon B, Siemeister G, Martiny-Baron G et al (1997) Vascular endothelial growth factor upregulates its receptor fms like tyrosine kinase (FLT-1). Cancer Res 57:5421–5425

    PubMed  CAS  Google Scholar 

  • Brandner B, Kurkela B, Vihko P, Kungl AJ (2006) Investigating the effect of VEGF glycosylation on GAG binding and protein folding. Biochem Biophys Res Commun 3:836–839

    Article  Google Scholar 

  • Cao Y (2005) Tumor angiogenesis and therapy. Biomed Pharmacother 59:S340–343

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P, Andras N, Ferreira V, Breier G et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439

    Article  PubMed  CAS  Google Scholar 

  • Chade AR, Bentley HD, Zhu X et al (2004) Antioxidant intervention prevents renal neovascularization in hypercholesterolemic pigs. Am Soc Nephrol 15:1816–1825

    Article  CAS  Google Scholar 

  • Chambon P, Weill JD, Mandel IL (1963) Nicotinamide mononucleotide activation of a new DNA- dependent polyadenylic acid synthesizing enzyme. Biochem Biophys Res Commun 11:39–43

    Article  PubMed  CAS  Google Scholar 

  • Chua CC, Hamdy RC, Chua BH (1998) Upregulation of Vascular endothelial growth factor by H2O2 in rat heart endothelial cells. Free Radic Biol Med 25:891–897

    Article  PubMed  CAS  Google Scholar 

  • D’Amours D, Desnoyers S, D’Silva I, Poirier GG (1999) Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. J Biochem 342(2):249–268

    Article  Google Scholar 

  • Davidovic L, Vodenicharov M, Affar EB, Poirier GG (2001) Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Exp Cell Res 268:7–13

    Article  PubMed  CAS  Google Scholar 

  • Dumount DJ, Fong GH, Puri MC et al (1995) Vascularization of the mouse embryo, a study of FLK-1, tck, tie and vascular EGF expression during development. Dev Dyn 203:80–92

    Article  Google Scholar 

  • Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 146:1029–1039

    PubMed  CAS  Google Scholar 

  • Ema M, Taya S, Yokotani N et al (1997) A novel bHLH –PAS factor with close sequence similarity to hypoxia inducible factor 1α regulates VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci USA 94:4273–4278

    Article  PubMed  CAS  Google Scholar 

  • Eola KK, Lymboussaki A, Taira S et al (1996) VEGF C receptor binding and pattern of expression with VEGFR 3 suggests a role in lymphatic vascular development. Development 122:3629–3837

    Google Scholar 

  • Ferrara N (1995) The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat 36:127–137

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N, Houck KA, Jakeman LB et al (1991) Vascular endothelial growth factor family of polypeptides. Cell Biochem 47:211–218

    Article  CAS  Google Scholar 

  • Ferrara N, Moore MW, Dowd M, Lu L, Hillan KJ et al (1996) Heterozygous embryonic lethality induced by targeted inactivation of VEGF gene. Nature 380:439–442

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N, Gerber HP, Le Couter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  PubMed  CAS  Google Scholar 

  • Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  • Gluzman-Poltorak Z, Cohen T, Herzog Y et al (2000) Neuropilin-2 is a receptor for the VEGF forms VEGF145 and VEGF165. J Biol Chem 275:18040–18045

    Google Scholar 

  • Gnarra JR (1996) Post translational regulation of vascular endothelial growth factor mRNA by the product of VHL tumor suppressor gene. Prac Natl Acad Sci USA 20:10589–10594

    Article  Google Scholar 

  • Hassa PO, Hottiger MO (2008) The diverse biological roles of mammalian PARPs, a small but powerful family of ply-ADP-ribose polymerases. Front Biosci 13:3046–3082

    Google Scholar 

  • Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70: 789–829

    Article  PubMed  CAS  Google Scholar 

  • Hermann J, Lerman LO, Mukhopadhyay D et al (2006) Angiogenesis in atherogenesis. Thromb Vasc Biol 26:1948–1957

    Article  Google Scholar 

  • Houck KA, Ferrara N, Winer J et al (1991) The vascular endothelial growth factor family identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endrocrinol 5:1806–1814

    Article  CAS  Google Scholar 

  • Huang LE, Bunn HF (2003) Hypoxia inducible factor and its biomedical relevance. J Biol Chem 278:19575–19578

    Google Scholar 

  • Joukov V, Alitalo K (1996) A novel vascular endothelial growth factor, VEGF C is a ligand for the FLT 4(VEGFR-3) and KDR(VEGFR-2) receptor kinases. EMBO J 15:290–298

    PubMed  CAS  Google Scholar 

  • Keck PJ, Connolly HSD et al (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309–1312

    Article  PubMed  CAS  Google Scholar 

  • Kim JK, Ferrara N (1993) Inhibition of vascular endothelial growth factor induced angiogenesis supresses tumor growth in vivo. Nature 362:841–844

    Article  PubMed  CAS  Google Scholar 

  • Kim MY, Zhang T, Kraus WL (2005) Poly(ADP-ribosyl)ation by PARP-1: ‘PAR- laying’ NAD+ into a nuclear signal. Genes Dev 19:1951–1967

    Article  PubMed  CAS  Google Scholar 

  • Kumar VB, Viji RI, Kiran MS, Sudhakaran PR (2007) Endothelial cell response to lactate: implications of PAR modification of VEGF. J Cell Physiol 211(2):477–485

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Gray A, Yuan J et al (1996) Vascular endothelial growth factor related protein: a ligand and specific activator of the tyrosine kinase receptor flt-4. Proc Natl Acad Sci USA 93:1988–1992

    Article  PubMed  CAS  Google Scholar 

  • Leung DW, Cachianes G, Kuang WJ et al (1989) Vascular endothelial growth factor is a secreted angiogenesis mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  • Levy NS, Chung S, Furneaux H et al (1998) Hypoxia stabilization of vascular endothelial growth factor mRNA by the RNA binding protein HuR. J Biol Chem 273:6417–6423

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Cox SR, Morita T, Kourembana S (1995) Hypoxia regulates VEGF gene expression in endothelial cells, identification of a 5′ enhancer. Circ Res 77:638–643

    Article  PubMed  CAS  Google Scholar 

  • Maglione D, Guerriero V, Viglietto G et al (1991) Isolation of human placenta cDNA coding for a protein related to vascular permeability factor. Proc Natl Acad Sci USA 88:9267–9271

    Article  PubMed  CAS  Google Scholar 

  • Mandriota SJ, Seghezzi G, Vassalli JD et al (1995) Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J Biol Chem 270:9709–9716

    Article  PubMed  CAS  Google Scholar 

  • Minchinko A, Salieda I, Bauer T, Caro J (1994) Hypoxia regulatory elements of human VEGF gene. Cell Mol Biol Res 40:35–39

    Google Scholar 

  • Modlich U, Kaup J, Augustin HG (1996) Cyclic angiogenesis and blood vessel regression in the ovary: blood vessel regression during luteolysis involves endothelial cell detachment and vessel occlusion. Lab Invest 74:771–780

    PubMed  CAS  Google Scholar 

  • Neufeld G, Tessler S, Gitay-Goren H et al (1994) Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 5:89–97

    Google Scholar 

  • Olofsson B, Pajusola K, von Euler G et al (1996) Genomic organization of the mouse and human genes for vascular endothelial growth factor B and characterization of a second splice isoforms. J Biol Chem 271:19310–19317

    Article  PubMed  CAS  Google Scholar 

  • Park JE, Killer GA, Ferrrara N (1993) The vascular endothelial growth factor isoforms: differential deposition into sub endothelial extra cellular matrix and bioavailability of extracellular matrix bound VEGF. Mol Biol Cell 4:1317–1326

    PubMed  CAS  Google Scholar 

  • Pepper MS, Ferrara N, Orci L, Montesano R (1991) VEGF induces plasminogen activators and plasminogen activator inhibitor 1 in microvascular endothelial cells. Biochem Biophys Res Commun 181:902–906

    Article  PubMed  CAS  Google Scholar 

  • Pepper MS, Ferrara N, Orci L, Montesano R (1992) Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 189:824–831

    Article  PubMed  CAS  Google Scholar 

  • Peretz D, Gitay-Goren H, Safran H et al (1992) Glycosylation of VEGF is not required for its mitogenic activity. Biochem Biophys Res Commun 182(3):1340–1347

    Article  PubMed  CAS  Google Scholar 

  • Plouet J, Schilling J, Gos Podarowicz D (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8(12):3801–3806

    PubMed  CAS  Google Scholar 

  • Ruf A, Mennissier de Murcia J, de Murcia G, Schulz GE (1996) Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken. Proc Natl Acad Sci USA 93:7481–7485

    Article  PubMed  CAS  Google Scholar 

  • Senger DR, Galli SJ, dvorak AM, Peruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promote accumulation of ascites fluid. Science 219:983–985

    Google Scholar 

  • Stacker SA, Stenvers K, Caesar C et al (1999) Biosynthesis of vascular endothelial growth factor D involves proteolytic processing which generates non covalent homodimers. J Biol Chem 274:32127–32136

    Article  PubMed  CAS  Google Scholar 

  • Stein I (1998) Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia. Mol Cell Biol 18(6):3112–3119

    PubMed  CAS  Google Scholar 

  • Tischler E, Abraham JA (1991) The human gene for vascular endothelial growth factor, multiple protein forms are encoded through alternative splicing of RNA. J Biol Chem 226:11947–11954

    Google Scholar 

  • Tulin A, Spradling A (2003) Chromatin loosening by poly(ADP) ribose polymerase (PARP) at Drosophila puff loci. Science 299:560–562

    Article  PubMed  CAS  Google Scholar 

  • Viji RI, Sameerkumar VB, Kiran MS, Sudhakaran PR (2008) Angiogenic response of endothelial cells to heparin-binding domain of fibronectin. Int J Biochem Cell Biol 40(2):215–226

    Article  PubMed  CAS  Google Scholar 

  • Xiong M, Elson G, Legarda D, Leibovich SL (1998) Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate and inducible nitric oxide synthase pathway. Am J Pathol 153:587–598

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors acknowledge support from University Grants Commission and Kerala State Council for Science, Technology, and Environment.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Kerala, Karyavattom, Thiruvananthapuram, 695 581, Kerala, India

    S. Binu, S. J. Soumya, V. B. S. Kumar & Perumana R. Sudhakaran

  2. Division of Haematology/Oncology, Cincinatti Children’s Hospital, 3333 Burnet Avenue, Cincinatti, OH, 40229-3039, USA

    V. B. S. Kumar

  3. School of Biological Sciences, Central University of Kerala, Riverside Transit Campus, Padannakkad, Nileswar, Kasaragod, 671 328, Kerala, India

    Perumana R. Sudhakaran

Authors
  1. S. Binu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. J. Soumya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. B. S. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Perumana R. Sudhakaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Perumana R. Sudhakaran .

Editor information

Editors and Affiliations

  1. Riverside Transit Campus, School of Biological Sciences, Central University of Kerala, Kasargod, 671328, Kerala, India

    Perumana R. Sudhakaran

  2. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, Delhi, India

    Avadhesha Surolia

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this paper

Cite this paper

Binu, S., Soumya, S.J., Kumar, V.B.S., Sudhakaran, P.R. (2012). Poly-ADP-Ribosylation of Vascular Endothelial Growth Factor and Its Implications on Angiogenesis. In: Sudhakaran, P., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 749. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3381-1_18

Download citation

Publish with us

Policies and ethics

Search

Navigation