A comparative study on the mechanism of the anticoagulant action of mollusc and mammalian heparins

Paiva, JoséF.; Santos, Elizeu A.; Jeske, Walter; Fareed, Jawed; Nader, Helena B.; Dietrich, Carl P.

doi:10.1016/0300-9629(94)00021-k

Cited by 5 publications

(10 citation statements)

References 13 publications

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“…The length and abundance of these two regions vary according to the origin of heparin. Thus, bovine lung heparin is extremely rich in the region susceptible to heparinase (36), whereas bovine intestinal heparin and mollusc heparins contain significant amounts of the region susceptible to heparitinase II (37)(38)(39)(40)(41). The estimated abundance of the two regions is shown in Figure 9.…”

Section: Heparin In Invertebratesmentioning

confidence: 99%

“…Besides the disaccharides depicted in the figure, other disaccharide units which occur in small amounts in the molecule have been identified such as disaccharides containing 3-O sulfated residues in the glucosamine moiety (42) and N-acetylated glucosamine (43). Besides being susceptible to specific enzymes the heparin from Anomalocardia brasiliana possesses all the other properties characteristic of heparin such as anticoagulant and other pharmacological activities (38,40) and chemical degradation (38). NMR spectroscopy has shown that the mollusc …”

Section: Heparin In Invertebratesmentioning

confidence: 99%

See 1 more Smart Citation

Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Nader

Sf²,

Ea³

et al. 1999

Braz J Med Biol Res

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The distribution and structure of heparan sulfate and heparin are briefly reviewed. Heparan sulfate is a ubiquitous compound of animal cells whose structure has been maintained throughout evolution, showing an enormous variability regarding the relative amounts of its disaccharide units. Heparin, on the other hand, is present only in a few tissues and species of the animal kingdom and in the form of granules inside organelles in the cytoplasm of special cells. Thus, the distribution as well as the main structural features of the molecule, including its main disaccharide unit, have been maintained through evolution. These and other studies led to the proposal that heparan sulfate may be involved in the cell-cell recognition phenomena and control of cell growth, whereas heparin may be involved in defense mechanisms against bacteria and other foreign materials. All indications obtained thus far suggest that these molecules perform the same functions in vertebrates and invertebrates.

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Section: Heparin In Invertebratesmentioning

confidence: 99%

Section: Heparin In Invertebratesmentioning

confidence: 99%

Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Nader

Sf²,

Ea³

et al. 1999

Braz J Med Biol Res

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“…Heparin has been isolated from a number of different species. [9][10][11][13][14][15][16]27,28 Although similar to the standard porcine mucosal heparin, heparins from other species also exhibit a number of distinct differences. Heparin isolated from mollusk, for example, has a relatively high mean molecular weight (22.5 kDa), an antifactor Xa/antifactor IIa ratio of less than 1, and contains up to 3 antithrombin binding sites per chain.…”

Section: Discussionmentioning

confidence: 99%

“…8 Isolation techniques similar to those used to make porcine heparin have shown that heparin is present in a number of marine species, including shrimp heads 9,10 and a variety of mollusks. [11][12][13][14] The biologic role of heparin in these species is unknown, but once these heparins are isolated, they display biologic activities similar to those of porcine mucosal heparin. 11 Studies in the late 1960s and early 1970s showed that skin from rats and hogs contains heparin.…”

mentioning

confidence: 99%

Isolation and Characterization of Heparin From Tuna Skins

Jeske

McDonald

Hoppensteadt

et al. 2007

Clin Appl Thromb Hemost

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This study characterized heparin isolated from tuna skins. Glycosaminoglycans were isolated from tuna skin after digestion using anion exchange resin. Heparin was eluted from the resin by sodium chloride gradient and was further fractionated by acetone fractionation. Anticoagulant activity was determined using the activated partial thromboplastin time and Heptest assays. Potency was determined using amidolytic antifactor IIa and antifactor Xa assays. The presence of heparin in the extracted tuna skin glycosaminoglycans was confirmed using (13)C-nuclear magnetic resonance. The activated partial thromboplastin time and Heptest clotting times were doubled at concentrations of about 4 and 1 microg/mL, respectively. The clotting time prolongation and antiprotease activity induced by tuna heparin was readily neutralized by 25 microg/mL protamine sulfate. These results demonstrate that biologically active heparin with properties similar to clinical grade heparin can be derived from tuna skin, a raw material with otherwise relatively little economic value.

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“…Hepariniike compounds, which are present in some invertebrates, result in high anticoagulant activity, and their structural properties are similar to mammalian heparins. A few differences, however, are observed (11-14~; Some compounds have a higher degree of binding with antithrombin III (ATIII), higher affinity to heparin, cofactor II (HCII), higher molecular weight, and higher anticoagulant activity (10,13). A heparinlike compound was isolated from the viscera of the shrimp, P. brasilien-;sa.~, by Dietfich et al (12).…”

Section: Discussionmentioning

confidence: 99%

Anticoagulant and Antiprotease Effects of a Novel Heparinlike Compound From Shrimp (Penaeus brasiliensis) and Its Neutralization by Heparinase I

Demir

Iqbal

Dietrich

et al. 2001

Clin Appl Thromb Hemost

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Heparin is usually obtained from mammalian organs, such as beef lung, beef mucosa, porcine mucosa, and sheep intestinal mucosa. Because of the increased use of heparin in the production of low-molecular-weight heparin (LMWH), there is a growing shortage of the raw material needed to produce LMWHs. A previous report described the structural features of a novel LMWH from the shrimp (Penaeus brasiliensis). In order to compare anticoagulant and antiprotease effects of this heparin, global anticoagulant tests, such as the prothrombin time, activated partial thromboplastin time, thrombin time, and Heptest, were used. Amidolytic anti-Xa and anti-IIa activities were also measured. The relative susceptibility of this heparin to flavobacterial heparinase was also evaluated. The United States Pharmacopeia (USP) potency of shrimp heparin (SH) was found to be 28 U/mg. SH produced a concentration-dependent prolongation of all of the clotting tests and exhibited marked inhibition of FXa and FIIa. Heparinase treatment resulted in a marked decrease of the anticoagulant effects and neutralized the in vitro anti-IIa actions. However, the anti-Xa activities were only partially neutralized. Protamine sulfate was only partially effective in neutralizing the anticoagulant and antithrombin effects of SH. SH also produced marked prolongation of activated clotting time, which was neutralized by heparinase but not by protamine sulfate. These results suggest that SH is a strong anticoagulant with comparable properties to mammalian heparins and can be used in the development of clinically useful antithrombotic-anticoagulant drugs.

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A comparative study on the mechanism of the anticoagulant action of mollusc and mammalian heparins

Cited by 5 publications

References 13 publications

Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates?

Isolation and Characterization of Heparin From Tuna Skins

Anticoagulant and Antiprotease Effects of a Novel Heparinlike Compound From Shrimp (Penaeus brasiliensis) and Its Neutralization by Heparinase I

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