Structural and hemostatic activities of a sulfated galactofucan from the brown alga Spatoglossum schroederi - An ideal antithrombotic agent?

Structural and hemostatic activities of a sulfated galactofucan from the brown alga Spatoglossum schroederi - An ideal antithrombotic agent?

Autor Rocha, Hugo Alexandre Oliveira Autor UNIFESP Google Scholar
Moraes, Fabio A. Autor UNIFESP Google Scholar
Trindade, Edvaldo da Silva Autor UNIFESP Google Scholar
Franco, CRC Google Scholar
Torquato, Ricardo José Soares Autor UNIFESP Google Scholar
Veiga, Silvio Sanches Autor UNIFESP Google Scholar
Valente, A. P. Google Scholar
Mourao, PAS Google Scholar
Leite, E. L. Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Dietrich, Carl Peter Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande Norte
Univ Fed Parana
Universidade Federal do Rio de Janeiro (UFRJ)
Resumo The brown alga Spatoglossum schroederi contains three fractions of sulfated polysaccharides. One of them was purified by acetone fractionation, ion exchange, and molecular sieving chromatography. It has a molecular size of 21.5 kDa and contains fucose, xylose, galactose, and sulfate in a molar ratio of 1.0:0.5:2.0:2.0 and contains trace amounts of glucuronic acid. Chemical analyses, methylation studies, and NMR spectroscopy showed that the polysaccharide has a unique structure, composed of a central core formed mainly by 4-linked beta-galactose units, partially sulfated at the 3-O position. Approximately 25% of these units contain branches of oligosaccharides (mostly tetrasaccharides) composed of 3-sulfated, 4-linked alpha-fucose and one or two nonsulfated, 4-linked beta-xylose units at the reducing and nonreducing end, respectively. This sulfated galacto-fucan showed no anticoagulant activity on several in vitro assays. Nevertheless, it had a potent antithrombotic activity on an animal model of experimental venous thrombosis. This effect is time-dependent, reaching the maximum 8 h after its administration compared with the more transient action of heparin. the effect was not observed with the desulfated molecule. Furthermore, the sulfated galactofucan was 2-fold more potent than heparin in stimulating the synthesis of an antithrombotic heparan sulfate by endothelial cells. Again, this action was also abolished by desulfation of the polysaccharide. Because this sulfated galactofucan has no anticoagulant activity but strongly stimulates the synthesis of heparan sulfate by endothelial cells, we suggested that this last effect may be related to the in vivo antithrombotic activity of this polysaccharide. in this case the highly sulfated heparan sulfate produced by the endothelial cells is in fact the antithrombotic agent. Our results suggested that this sulfated galactofucan may have a potential application as an antithrombotic drug.
Idioma Inglês
Data de publicação 2005-12-16
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 280, n. 50, p. 41278-41288, 2005.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Biochemistry Molecular Biology Inc
Extensão 41278-41288
Fonte http://dx.doi.org/10.1074/jbc.M501124200
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000233866900022
Endereço permanente http://repositorio.unifesp.br/handle/11600/28596

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