Structure and Anticoagulant Activity of Sulfated Galactans

Farias, Wladimir Ronald Lobo; Valente, Ana Paula; Pereira, M. S.; Mourāo, Paulo A.S.

doi:10.1074/jbc.m002422200

Cited by 263 publications

(107 citation statements)

References 39 publications

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“…Like the native sulfated galactan, the subfractions present very complex 1 H NMR spectra, due to a heterogeneous sulfation pattern. Nevertheless, the observed signals can be clearly assigned to specific structures, as described in a previous study (13). Thus, the signals at ϳ5.7 and 5.4 to 5.2 ppm are attributed to anomeric protons of 2,3-di-sulfated ␣-galactose units and 2-or non-sulfated units, respectively.…”

Section: Anticoagulant Activity Of Sulfated Galactans: Does the Molecmentioning

confidence: 85%

“…The purity of each fraction was checked by agarose gel electrophoresis and NMR spectroscopy, as described (13,23,26). Dermatan sulfate from bovine intestinal mucosa and chondroitin 6-sulfate from shark cartilage were from Sigma.…”

Section: Methodsmentioning

confidence: 99%

“…1A). The potent anticoagulant activity of this algal galactan (potency similar to that of unfractionated heparin) was attributed mostly to the 2,3-di-sulfated units (13).…”

mentioning

confidence: 99%

“…They contain a variety of sulfated galactans (11)(12)(13) and sulfated fucans (14 -17). They are among the most abundant non-mammalian sulfated polysaccharides found in nature.…”

mentioning

confidence: 99%

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Antithrombin-mediated Anticoagulant Activity of Sulfated Polysaccharides

Melo

Pereira

Foguel

et al. 2004

Journal of Biological Chemistry

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148

108

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We investigated the mechanisms of anticoagulant activity mediated by sulfated galactans. The anticoagulant activity of sulfated polysaccharides is achieved mainly through potentiation of plasma cofactors, which are the natural inhibitors of coagulation proteases. Our results indicated the following. 1) Structural requirements for the interaction of sulfated galactans with coagulation inhibitors and their target proteases are not merely a consequence of their charge density. 2) The structural basis of this interaction is complex because it involves naturally heterogeneous polysaccharides but depends on the distribution of sulfate groups and on monosaccharide composition. 3) Sulfated galactans require significantly longer chains than heparin to achieve anticoagulant activity. 4) Possibly, it is the bulk structure of the sulfated galactan, and not a specific minor component as in heparin, that determines its interaction with antithrombin. 5) Sulfated galactans of ϳ15 to ϳ45 kDa bind to antithrombin but are unable to link the plasma inhibitor and thrombin. This last effect requires a molecular size above 45 kDa. 6) Sulfated galactan and heparin bind to different sites on antithrombin. 7) Sulfated galactans are less effective than heparin at promoting antithrombin conformational activation. Overall, these observations indicate that a different mechanism predominates over the conformational activation of antithrombin in ensuring the antithrombin-mediated anticoagulant activity of the sulfated galactans. Possibly, sulfated galactan connects antithrombin and thrombin, holding the protease in an inactive form. The conformational activation of antithrombin and the consequent formation of a covalent complex with thrombin appear to be less important for the anticoagulant activity of sulfated galactan than for heparin. Our results demonstrate that the paradigm of heparin-antithrombin interaction cannot be extended to other sulfated polysaccharides. Each type of polysaccharide may form a particular complex with the plasma inhibitor and the target protease.

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Section: Anticoagulant Activity Of Sulfated Galactans: Does the Molecmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

“…1A). The potent anticoagulant activity of this algal galactan (potency similar to that of unfractionated heparin) was attributed mostly to the 2,3-di-sulfated units (13).…”

mentioning

confidence: 99%

“…They contain a variety of sulfated galactans (11)(12)(13) and sulfated fucans (14 -17). They are among the most abundant non-mammalian sulfated polysaccharides found in nature.…”

mentioning

confidence: 99%

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Antithrombin-mediated Anticoagulant Activity of Sulfated Polysaccharides

Melo

Pereira

Foguel

et al. 2004

Journal of Biological Chemistry

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148

108

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“…In addition to egg jelly coats, these polymers are also found in the extracellular matrix of the adult body wall in echinoderms (30). The egg FSPs mediate signal transduction in sperm and are also potent inhibitors of human blood coagulation (11,31). Their biosynthesis has not been studied, and glycosidases that degrade them have not been described.…”

Section: Discussionmentioning

confidence: 99%

High Molecular Mass Egg Fucose Sulfate Polymer Is Required for Opening Both Ca2+ Channels Involved in Triggering the Sea Urchin Sperm Acrosome Reaction

Hirohashi

Vacquier

2002

Journal of Biological Chemistry

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A linear fucose sulfate polymer (FSP), >106 daltons, is a major component of sea urchin egg jelly. FSP induces the sperm acrosome reaction (AR), an exocytotic process required for animal fertilization. Two Ca 2؉ channels activate during AR induction, the first opens 1 s after FSP addition, and the second opens 5 s after the first. Mild acid hydrolysis of FSP results in a linear decrease in polymer size. The ability of FSP to induce the AR and activate sperm Ca 2؉ channels decreases with increasing time of hydrolysis. Hydrolyzed FSP of ϳ60 kDa blocks intact FSP from inducing the AR. At 44 g/ml hydrolyzed FSP, Ca 2؉ entry into sperm is almost equal to that occurring in 3.8 g/ml intact FSP; however the AR is not induced. The sperm acrosome reaction (AR) 1 is required for animal fertilization and is a potential target for the development of novel methods of non-hormonal contraception. Sea urchin spermatozoa are ideal for studying signal transduction underlying the animal sperm AR because they can be obtained as pure cells in vast quantities at low cost. The AR is triggered when sperm contact the jelly layer surrounding the egg (EJ). Morphologically, the AR involves the exocytosis of the acrosomal vesicle and the polymerization of actin to form the acrosomal process; both events are required for sperm to bind to and fuse with eggs. Physiologically, the AR requires the influx of Ca 2ϩ and Na ϩ and the efflux of H ϩ and K ϩ ions (1, 2). There are two plasma membrane Ca 2ϩ channels involved in AR induction: the first is receptor-operated and opens 1 s after sperm contact EJ, the second opens 5 s after the first in response to increased intracellular pH (pH i ). The second channel can also transport Mn 2ϩ (2-4). The Ca 2ϩ channel blocker nisoldipine does not block Mn 2ϩ movement through the second channel but does block the first channel and hence also blocks the AR (3). Eighty percent of the mass of sea urchin EJ is a fucose sulfate polymer (FSP) of Ͼ1 million daltons (5). Purified FSP, having no amino acid content, induces the AR (5, 6). However, oligosaccharides of EJ glycoproteins substantially potentiate the FSP-induced AR, suggesting there is more than one receptor system regulating ion channels that trigger the AR (7). 2FSP is a linear polymer of ␣-L-1,3-fucose with a species-specific pattern of sulfation of the fucosyl residues (8). The sulfation pattern is responsible for FSP's species-specific induction of the AR (9, 10). FSP is also a potent inhibitor of human blood coagulation through its high affinity binding to heparin cofactor II (11).Receptor for egg jelly-1 (REJ1) is a 1450-amino acid glycoprotein located in the plasma membrane over the sea urchin sperm acrosomal vesicle and also on the sperm flagellum. Available data support the hypothesis that REJ1 is at least one of the sperm receptors for FSP (6, 12). Purified REJ1 neutralizes the AR activity of EJ (12). An affinity column of REJ1 binds only FSP when crude EJ is applied (6). Monoclonal antibodies to REJ1 induce Ca 2ϩ influx into sperm (13) and induce...

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Bioactive Polysaccharides from Marine Macroalgae

Khora

Navya

2020

Encyclopedia of Marine Biotechnology

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Structure and Anticoagulant Activity of Sulfated Galactans

Cited by 263 publications

References 39 publications

Antithrombin-mediated Anticoagulant Activity of Sulfated Polysaccharides

Antithrombin-mediated Anticoagulant Activity of Sulfated Polysaccharides

High Molecular Mass Egg Fucose Sulfate Polymer Is Required for Opening Both Ca2+ Channels Involved in Triggering the Sea Urchin Sperm Acrosome Reaction

Bioactive Polysaccharides from Marine Macroalgae

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