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Tunicate Heparan Sulfate Enriched in 2-Sulfated β-Glucuronic Acid: Structure, Anticoagulant Activity, and Inhibitory Effect on the Binding of Human Colon Adenocarcinoma Cells to Immobilized P-Selectin.

  • Abreu WS Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. wallace.s.abreu@gmail.com.
  • Soares PAG Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. paulogsoares@hucff.ufrj.br.
  • Motta JM Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. jmotta@bioqmed.ufrj.br.
  • Kozlowski EO Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil.
  • Teixeira FCOB Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. felipebrito7@gmail.com.
  • Soares MA Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. mariana.alsoares@gmail.com.
  • Borsig L Institute of Physiology, University of Zurich and Zurich Center for Integrative Human Physiology, 8057 Zurich, Switzerland. lborsig@access.uzh.ch.
  • Mourão PAS Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. pmourao@hucff.ufrj.br.
  • Pavão MSG Programa de Glicobiologia, Instituto de Bioquímica Médica Leopoldo de Meis and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-913 Rio de Janeiro, RJ, Brazil. mpavao@hucff.ufrj.br.
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  • 2019-06-20
Published in:
  • Marine drugs. - 2019
P-selectin
ascidian glycosaminoglycans
cancer
coagulation
heparan sulfate
marine biology
nuclear magnetic resonance
Adenocarcinoma
Animals
Anticoagulants
Cell Line, Tumor
Colon
Colonic Neoplasms
Glucuronates
Glucuronic Acid
Glycosaminoglycans
Heparin
Heparitin Sulfate
Humans
P-Selectin
Urochordata
English Heparin or highly sulfated heparan sulfate (HS) has been described in different invertebrates. In ascidians (Chordata-Tunicata), these glycosaminoglycans occur in intracellular granules of oocyte accessory cells and circulating basophil-like cells, resembling mammalian mast cells and basophils, respectively. HS is also a component of the basement membrane of different ascidian organs. We have analyzed an HS isolated from the internal organs of the ascidian Phallusia nigra, using solution 1H/13C NMR spectroscopy, which allowed us to identify and quantify the monosaccharides found in this glycosaminoglycan. A variety of α-glucosamine units with distinct degrees of sulfation and N-acetylation were revealed. The hexuronic acid units occur both as α-iduronic acid and β-glucuronic acid, with variable sulfation at the 2-position. A peculiar structural aspect of the tunicate HS is the high content of 2-sulfated β-glucuronic acid, which accounts for one-third of the total hexuronic acid units. Another distinct aspect of this HS is the occurrence of high content of N-acetylated α-glucosamine units bearing a sulfate group at position 6. The unique ascidian HS is a potent inhibitor of the binding of human colon adenocarcinoma cells to immobilized P-selectin, being 11-fold more potent than mammalian heparin, but almost ineffective as an anticoagulant. Thus, the components of the HS structure required to inhibit coagulation and binding of tumor cells to P-selectin are distinct. Our results also suggest that the regulation of the pathway involved in the biosynthesis of glycosaminoglycans suffered variations during the evolution of chordates.
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  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/47546
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