Structure and Biological Activity of Heparin

Casu, Benito

doi:10.1016/s0065-2318(08)60067-0

Cited by 444 publications

(245 citation statements)

References 395 publications

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“…For fucoidan, a sulfated polymer of ␣-(133)-linked L-fucose, it has been estimated that most of the sulfated esters are located on the C-4 position (37). However, in the case of heparin the carbohydrate backbone consists of hexuronic acid (D-glucuronic or L-iduronic) ␤-(134)-linked to Dglucosamine units, with variable location of the sulfated substituents, encompassing: N-sulfation of free amino groups at C-2 of glucosamine, O-sulfation at C-2 of iduronic acid residues, and O-sulfation at C-6 of glucosamine units (38). Dextran sulfate is a ␣-(136)-linked D-glucose polymer that is highly Osulfated.…”

Section: Discussionmentioning

confidence: 99%

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

Ortega-Barrı́a

Boothroyd²

1999

Journal of Biological Chemistry

106

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Toxoplasma gondii is one of the most widespread parasites of humans and animals. The parasite has a remarkable ability to invade a broad range of cells within its mammalian hosts by mechanisms that are poorly understood at the molecular level. This broad host cell specificity suggests that adhesion should involve the recognition of ubiquitous surface-exposed host molecules or, alternatively, the presence of various parasite attachment molecules able to recognize different host cell receptors. We have discovered a sugar-binding activity (lectin) in tachyzoites of T. gondii that plays a role in vitro in erythrocyte agglutination and infection of human fibroblasts and epithelial cells. The ability to agglutinate erythrocytes can be reversed by a variety of soluble glycoconjugates, of which heparin, fucoidan, and dextran sulfate were the most effective. Interestingly, infectivity of tachyzoites for human foreskin fibroblasts, cells that are commonly used to grow T. gondii in vitro, was increased by low concentrations of the sulfated glycoconjugates that inhibited hemagglutination activity (i.e. dextran sulfate and fucoidan) whereas high concentrations inhibited parasite infection. Furthermore, inhibition of glycosaminoglycan biosynthesis and sulfation on the host cells reduced Toxoplasma infectivity. Finally, Toxoplasma tachyzoites showed a reduced ability to infect epithelial cell mutants deficient in the biosynthesis of surface proteoglycans. The probable identity of the hemagglutinin(s) was investigated by 1) direct binding of red blood cells to filter blots of Toxoplasma proteins separated by polyacrylamide gel electrophoresis, and 2) binding of metabolically labeled parasite proteins to fixed mammalian cells. Three parasite bands were thus identified as candidate adhesins. These results suggest that attachment of T. gondii to its target cell is mediated by parasite lectins and that sulfated sugars on the surface of host cells may function as a key parasite receptor.

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Section: Discussionmentioning

confidence: 99%

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

Ortega-Barrı́a

Boothroyd²

1999

Journal of Biological Chemistry

106

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“…These reactions also produce HS inact that lacks the primary AT-binding domain but contains all the other monosaccharide sequences including 3-O-sulfated residues (12,13). Although HS act constitutes only 1-10% of HS total , the relative abundance of this polysaccharide is greater by at least 10-fold than would be predicted by completely random assembly of disaccharide constituents (14). These observations suggest that production of the AT-binding site sequence requires the coordinated action of several biosynthetic enzymes.…”

mentioning

confidence: 99%

The Retinoic Acid and cAMP-dependent Up-regulation of 3-O-Sulfotransferase-1 Leads to a Dramatic Augmentation of Anticoagulantly Active Heparan Sulfate Biosynthesis in F9 Embryonal Carcinoma Cells

Zhang

Schwartz

Miller

et al. 1998

Journal of Biological Chemistry

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“…Since the first synthesis of heparin (McLean, 1916) a long-lasting debate has ran regarding its inner structure, as well as about its anticoagulant properties (Casu, 1985(Casu, , 1989. Heparin is extraordinary because of its variability.…”

Section: Heparinmentioning

confidence: 99%

Heparin and its derivatives in the treatment of arterial thrombosis: a review

Dvořák¹,

Vlašín²,

Dvorakova³

et al. 2010

Vet. Med. - Czech

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Arterial occlusion due to thrombosis caused by ruptured atherosclerotic plaques (Baba et al., 1975) has been recognized as a major cause of morbidity and mortality in western populations. Thrombosis may occur in various sections of arterial circulation, peripheral arteries of the limbs, coronary arteries, brain arteries, or both major and minor vessels within the abdominal cavity. The ultimate consequence is varying degrees of organ failure, mostly of ischemic origin. Arterial thrombosis represents a continuous problem, debilitating patients and decreasing their quality of life. Moreover, along with chronic heart failure, it can significantly decrease patient life expectancy. Arterial thrombosis results in ischemia, with serious systemic consequences, such as metabolic breakdown. The major goal of treatment remains fast and efficient recanalization -surgical, interventional or thrombolytic. To be able to prevent acute reocclusion with severe consequences (rhabdomyolysis, compartment syndrome, excessive tissue necrosis leading to limb amputation, etc.), several adjunctive treatment regimens have been advocated. Among others, thrombin inhibitors and platelet inhibitors have been widely used for both prophylaxis and adjunctive treatment. Direct thrombin inhibitors and antithrombin stimulators have been recognized as typical antithrombotic drugs. Direct (antithrombin-independent) thrombin inhibitors can be divided into two main categories: monovalent, active site inhibitors (argatroban, efegatran, inovastan, melagatran) and bivalent (hirudin, hirugen, hirulog, bivalirudin), while antithrombin stimulators represent standard (unfractionated) heparin (UFH) and its depolymerizing products -low molecular weight heparins (LMWH's). Recently, a clear change in the main use of heparin, as well as low-molecular weight heparins has been advocated representing a shift from treatment and prophylaxis of deep vein thrombosis to prophylaxis of thromboembolic disease following vascular, cardiovascular or orthopedic surgery, treatment of unstable angina and prevention of acute myocardial infarction. The main effect of heparins lies in their anticoagulant activity. Heparins are involved in different pathways of the coagulation cascade with anticoagulant, antithrombotic, profibrinolytic, anti-aggregative, as well as anti-inflammatory effects. Moreover, there is a little doubt about their anti-proliferative and anti-ischemic activity (Penka and Bulikova, 2006). Unlike standard heparin, low-molecular weight heparins do not affect the patient's general coagulation profile. Obviously, the difference in molecular weight results in different pharmacokinetic and pharmacodynamic properties of the agents.Key words: coagulation; arterial thrombosis; standard heparin; low-molecular weight heparins List of abbreviations ABI = axillary/...index, t-PA = tissue-type plasminogen activator, ADP = adenosin diphosphate, AG = angiography, AMI = acute myocardial infarction, APSAC = acylated plasminogen streptokinase activator complex, APTT = acti...

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Structure and Biological Activity of Heparin

Cited by 444 publications

References 395 publications

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

A Toxoplasma Lectin-like Activity Specific for Sulfated Polysaccharides Is Involved in Host Cell Infection

The Retinoic Acid and cAMP-dependent Up-regulation of 3-O-Sulfotransferase-1 Leads to a Dramatic Augmentation of Anticoagulantly Active Heparan Sulfate Biosynthesis in F9 Embryonal Carcinoma Cells

Heparin and its derivatives in the treatment of arterial thrombosis: a review

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