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|Type:||Artigo de periódico|
|Title:||Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [-> 4IdoA (2-Sulfate)beta-1 -> 3GalNAc(4-Sulfate)beta-1 ->] motifs in dermatan sulfate on heparin cofactor II activity|
|Abstract:||Background: Previously, we have reported the presence of highly sulfated dermatans in solitary ascidians from the orders Phlebobranchia (Phallusia nigra) and Stolidobranchia (Halocynthia pyriformis and Styela plicata). Despite the identical disaccharide backbone, consisting of [-> 4IdoA(2S)beta-1 -> 3GalNAc beta-1 ->], those polymers differ in the position of sulfation on the N-Acetyl galactosamine, which can occur at carbon 4 or 6. We have shown that position rather than degree of sulfation is important for heparin cofactor II activity. As a consequence, 2,4- and 2,6-sulfated dermatans have high and low heparin cofactor II activities, respectively. In the present study we extended the disaccharide analysis of ascidian dermatan sulfates to additional species of the orders Stolidobranchia (Herdmania pallida, Halocynthia roretzi) and Phlebobranchia (Ciona intestinalis), aiming to investigate how sulfation evolved within Tunicata. In addition, we analysed how heparin cofactor II activity responds to dermatan sulfates containing different proportions of 2,6- or 2,4-disulfated units. Results: Disaccharide analyses indicated a high content of disulfated disaccharide units in the dermatan sulfates from both orders. However, the degree of sulfation decreased from Stolidobranchia to Phlebobranchia. While 76% of the disaccharide units in dermatan sulfates from stolidobranch ascidians are disulfated, 53% of disulfated disaccharides are found in dermatan sulfates from phlebobranch ascidians. Besides this notable difference in the sulfation degree, dermatan sulfates from phlebobranch ascidians contain mainly 2,6-sulfated disaccharides whereas dermatan sulfate from the stolidobranch ascidians contain mostly 2,4-sulfated disaccharides, suggesting that the biosynthesis of dermatan sulfates might be differently regulated during tunicates evolution. Changes in the position of sulfation on N-acetylgalactosamine in the disaccharide [-> 4IdoA(2-Sulfate)beta-1 -> 3GalNAc beta-1 ->] modulate heparin cofactor II activity of dermatan sulfate polymers. Thus, high and low heparin cofactor II stimulating activity is observed in 2,4-sulfated dermatan sulfates and 2,6-sulfated dermatan sulfates, respectively, confirming the clear correlation between the anticoagulant activities of dermatan sulfates and the presence of 2,4-sulfated units. Conclusions: Our results indicate that in ascidian dermatan sulfates the position of sulfation on the GalNAc in the disaccharide [-> 4IdoA(2S)beta-1 -> 3GalNAc beta-1 ->] is directly related to the taxon and that the 6-O sulfation is a novelty apparently restricted to the Phlebobranchia. We also show that the increased content of [-> 4IdoA(2S)beta-1 -> 3GalNAc (4S)beta-1 ->] disaccharide units in dermatan sulfates from Stolidobranchia accounts for the increased heparin cofactor II stimulating activity.|
|Editor:||Biomed Central Ltd|
|Citation:||Bmc Biochemistry. Biomed Central Ltd, v. 12, 2011.|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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