Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities

Roberto J. C. Fonseca; Stephan-Nicollas M. C. G. Oliveira; Fábio R. Melo; Maria G. Pereira; Norma M. B. Benevides; Paulo A. S. Mourão

doi:10.1160/TH07-10-0603

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 99(03): 539-545
DOI: 10.1160/TH07-10-0603

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities

Roberto J. C. Fonseca

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Stephan-Nicollas M. C. G. Oliveira

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Fábio R. Melo

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Maria G. Pereira

²Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil

,

Norma M. B. Benevides

²Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil

,

Paulo A. S. Mourão

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

› Institutsangaben

Abstract

Summary

We compared sulfated galactans (SGs) from two species of red algae using specific coagulation assays and experimental models of thrombosis.These polysaccharides have an identical saccharide structure and the same size chain, but with slight differences in their sulfation patterns.As a consequence of these differences, the two SGs differ in their anticoagulant and venous antithrombotic activities.SG from G.crinale exhibits procoagulant and prothrombotic effects in low doses (up to 1.0 mg/kg body weight), but in high doses (>1.0 mg/kg) this polysaccharide inhibits both venous and arterial thrombosis in rats and prolongs ex-vivo recalcification time. In contrast, SG from B. occidentalis is a very potent anticoagulant and antithrombotic compound in low doses (up to 0.5 mg/kg body weight), inhibiting venous experimental thrombosis and prolonging ex-vivo recalcification time, but these effects are reverted in high doses. Only at high doses (>1.0 mg/kg) the SG from B. occidentalis inhibits arterial thrombosis. As with heparin, SG from G. crinale does not activate factor XII, while the polysaccharide from B. occidentalis activates factor XII in high concentrations, which could account for its procoagulant effect at high doses on rats. Both SGs do not modify bleeding time in rats.These results indicate that slight differences in the proportions and/or distribution of sulfated residues along the galactan chain may be critical for the interaction between proteases, inhibitors and activators of the coagulation system, resulting in a distinct pattern in anti- and procoagulant activities and in the antithrombotic action.

Keywords

Sulfated galactans - anticoagulant - antithrombotic - marine red alga - sulfation pattern

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Referenzen

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