Abstract
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.
Highlights
Heparan sulfate (HS) is a sulfated glycosaminoglycan present in virtually all animal species [1,2].It has a complex and diverse structure, which varies according to cell type and differentiation.Mammalian heparan sulfate (HS) chains are formed by repeating disaccharide units, consisting of β-D-glucuronicMar
We showed that the ascidian HS is enriched in 2-sulfated GlcA and 6-sulfated N-acetylated GlcN units; it does not inhibit coagulation but is 11-fold more active than mammalian heparin as an inhibitor of the binding of human colon adenocarcinoma cells to P-selectin
Total glycans from P. nigra were extracted from the viscera of the ascidian
Summary
Heparan sulfate (HS) is a sulfated glycosaminoglycan present in virtually all animal species [1,2]. In ascidians (Chordata-Urochordata), known as sea-squirts, solitary species like the stolidobranchia Styela plicata and the phlebobranchia Phallusia nigra are rich in glycosaminoglycans such as dermatan sulfate (DS) and heparin/HS [5,6,7,8] In both ascidians, the DSs are formed by disulfated disaccharide units composed exclusively by IdoA 2-sulfated. The structure of the heparin/HS polymers isolated from S. plicata had been previously studied by disaccharide analysis and multi-dimensional nuclear magnetic resonance (NMR) techniques These studies revealed that the disaccharide units of the ascidian heparin/HS are formed exclusively by IdoA 2-sulfated, linked to N-sulfated GlcN with different percentages of 6-sulfation (38–100%). We showed that the ascidian HS is enriched in 2-sulfated GlcA and 6-sulfated N-acetylated GlcN units; it does not inhibit coagulation but is 11-fold more active than mammalian heparin as an inhibitor of the binding of human colon adenocarcinoma cells to P-selectin
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