Glycobiology, 2000, Vol. 10, No. 6 577-586
© 2000 Oxford University Press
A novel role for nitric oxide in the endogenous degradation of heparan sulfate during recycling of glypican-1 in vascular endothelial cells
Department of Cell and Molecular Biology 1, Lund University, S-221 00 Lund, Sweden
We show here that the endothelial cell-line ECV 304 expresses the heparan sulfate proteoglycan glypican-1. The predominant cellular glycoform carries truncated side-chains and is accompanied by heparan sulfate oligosaccharides. Treatment with brefeldin A results in accumulation of a glypican proteoglycan with full-size side-chains while the oligosaccharides disappear. During chase the glypican proteoglycan is converted to partially degraded heparan sulfate chains and chain-truncated proteoglycan, both of which can be captured by treatment with suramin. The heparan sulfate chains in the intact proteoglycan can be depolymerized by nitrite-dependent cleavage at internally located N-unsubstituted glucosamine moieties. Inhibition of NO-synthase or nitrite-deprivation prevents regeneration of intact proteoglycan from truncated precursors as well as formation of oligosaccharides. In nitrite-deprived cells, formation of glypican proteoglycan is restored when NO-donor is supplied. We propose that, in recycling glypican-1, heparan sulfate chains are cleaved at or near glucosamines with unsubstituted amino groups. NO-derived nitrite is then required for the removal of short, nonreducing terminal saccharides containing these N-unsubstituted glucosamine residues from the core protein stubs, facilitating re-synthesis of heparan sulfate chains.
1 To whom correspondence should be addressed at: Department of Cell and Molecular Biology 1, POB 94, S-221 00 Lund, Sweden
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Vanpouille, A. Deligny, M. Delehedde, A. Denys, A. Melchior, X. Lienard, M. Lyon, J. Mazurier, D. G. Fernig, and F. Allain The Heparin/Heparan Sulfate Sequence That Interacts with Cyclophilin B Contains a 3-O-Sulfated N-Unsubstituted Glucosamine Residue J. Biol. Chem., August 17, 2007; 282(33): 24416 - 24429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mani, F. Cheng, and L.-A. Fransson Heparan Sulfate Degradation Products Can Associate with Oxidized Proteins and Proteasomes J. Biol. Chem., July 27, 2007; 282(30): 21934 - 21944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mani, S. Sandgren, J. Lilja, F. Cheng, K. Svensson, L. Persson, and M. Belting HIV-Tat protein transduction domain specifically attenuates growth of polyamine deprived tumor cells Mol. Cancer Ther., February 1, 2007; 6(2): 782 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mani, F. Cheng, and L.-A. Fransson Constitutive and vitamin C-induced, NO-catalyzed release of heparan sulfate from recycling glypican-1 in late endosomes Glycobiology, December 1, 2006; 16(12): 1251 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mani, F. Cheng, and L.-A. Fransson Defective nitric oxide-dependent, deaminative cleavage of glypican-1 heparan sulfate in Niemann-Pick C1 fibroblasts Glycobiology, August 1, 2006; 16(8): 711 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Girardin, S. HajMohammadi, B. Birmele, A. Helisch, N. W. Shworak, and A. I. de Agostini Synthesis of Anticoagulantly Active Heparan Sulfate Proteoglycans by Glomerular Epithelial Cells Involves Multiple 3-O-Sulfotransferase Isoforms and a Limiting Precursor Pool J. Biol. Chem., November 11, 2005; 280(45): 38059 - 38070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mani, F. Cheng, S. Sandgren, J. van den Born, B. Havsmark, K. Ding, and L.-A. Fransson The heparan sulfate-specific epitope 10E4 is NO-sensitive and partly inaccessible in glypican-1 Glycobiology, July 1, 2004; 14(7): 599 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mani, M. Belting, U. Ellervik, N. Falk, G. Svensson, S. Sandgren, F. Cheng, and L.-A. Fransson Tumor attenuation by 2(6-hydroxynaphthyl)-{beta}-D-xylopyranoside requires priming of heparan sulfate and nuclear targeting of the products Glycobiology, May 1, 2004; 14(5): 387 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Belting, K. Mani, M. Jonsson, F. Cheng, S. Sandgren, S. Jonsson, K. Ding, J.-G. Delcros, and L.-A. Fransson Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells: A PIVOTAL ROLE FOR NITROSOTHIOL-DERIVED NITRIC OXIDE J. Biol. Chem., November 21, 2003; 278(47): 47181 - 47189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mani, F. Cheng, B. Havsmark, M. Jonsson, M. Belting, and L.-A. Fransson Prion, Amyloid {beta}-derived Cu(II) Ions, or Free Zn(II) Ions Support S-Nitroso-dependent Autocleavage of Glypican-1 Heparan Sulfate J. Biol. Chem., October 3, 2003; 278(40): 38956 - 38965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Westling and U. Lindahl Location of N-Unsubstituted Glucosamine Residues in Heparan Sulfate J. Biol. Chem., December 13, 2002; 277(51): 49247 - 49255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cheng, K. Mani, J. van den Born, K. Ding, M. Belting, and L.-A. Fransson Nitric Oxide-dependent Processing of Heparan Sulfate in Recycling S-Nitrosylated Glypican-1 Takes Place in Caveolin-1-containing Endosomes J. Biol. Chem., November 8, 2002; 277(46): 44431 - 44439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ding, K. Mani, F. Cheng, M. Belting, and L.-A. Fransson Copper-dependent Autocleavage of Glypican-1 Heparan Sulfate by Nitric Oxide Derived from Intrinsic Nitrosothiols J. Biol. Chem., August 30, 2002; 277(36): 33353 - 33360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ding, S. Sandgren, K. Mani, M. Belting, and L.-A. Fransson Modulations of Glypican-1 Heparan Sulfate Structure by Inhibition of Endogenous Polyamine Synthesis. MAPPING OF SPERMINE-BINDING SITES AND HEPARANASE, HEPARIN LYASE, AND NITRIC OXIDE/NITRITE CLEAVAGE SITES J. Biol. Chem., December 7, 2001; 276(50): 46779 - 46791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ding, M. Jonsson, K. Mani, S. Sandgren, M. Belting, and L.-A. Fransson N-Unsubstituted Glucosamine in Heparan Sulfate of Recycling Glypican-1 from Suramin-treated and Nitrite-deprived Endothelial Cells. MAPPING OF NITRIC OXIDE/NITRITE-SUSCEPTIBLE GLUCOSAMINE RESIDUES TO CLUSTERED SITES NEAR THE CORE PROTEIN J. Biol. Chem., February 2, 2001; 276(6): 3885 - 3894. [Abstract] [Full Text] [PDF]
|
|