Desialylation of fibrinogen with neuraminidase. Kinetic and clotting studies

Dı́az-Mauriño, Teresa; Castro, C. Elizabeth; Albert, Armando

doi:10.1016/0049-3848(82)90057-3

Cited by 17 publications

(7 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other approaches have also been used in trying to establish the function of carbohydrate in the fibrin assembly process, either removing the sialic acid groups with neuraminidase or removing the whole carbohydrate by glycosidase [8,25,30]. In both cases, it was found that there was a dramatic increase in the rate of fibrin assembly, giving rise to more porous clots made up of thicker fibers that were less branched.…”

Section: Discussionmentioning

confidence: 99%

The effects of additional carbohydrate in the coiled‐coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aα Arg141→Ser with extra glycosylation)

Marchi

Arocha-Piñango

Nagy

et al. 2004

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Fibrinogen Lima is an abnormal fibrinogen with an Aa Arg141 fi Ser substitution resulting in an extra N-glycosylation at Aa Asn139, which seems to be responsible for the impairment of fibrin polymerization. We have studied the polymerization and properties of clots made from both plasma and purified fibrinogen of both the homozygous and heterozygous forms. The clot permeation studies with both plasma and purified protein revealed a normal flux through the network for the heterozygous form but very decreased permeation in the homozygous form. Consistent with turbidity results, the clot network of the homozygous form, seen by scanning electron microscopy, was tight and composed of thin fibers, with many branch points, while the appearance of clots from the heterozygous form was similar to that of control clots, but in both cases the fibers were more curved than those of control clots. The rheological properties of clots from the homozygous form were also altered, with rigidity being increased in plasma clots, but decreased in the purified system, a consequence of the balance between numbers of branch points and fiber curvature. From these results it seems that the extra carbohydrate moiety, located in the a coiled-coil region close to the bC domains, impairs the protofibril lateral association process, giving rise to thinner, more curved fibers, with the structural anomalies being most pronounced in the clots from the homozygous plasma. These studies support a model for fibrin polymerization in which the bC-bC interactions are involved in lateral aggregation.

show abstract

Section: Discussionmentioning

confidence: 99%

The effects of additional carbohydrate in the coiled‐coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aα Arg141→Ser with extra glycosylation)

Marchi

Arocha-Piñango

Nagy

et al. 2004

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Binding of galectin-1 was assayed using asialofibrin films onto plastic microwells. Asialofibrinogen was obtained from human fibrinogen (Kabi) by treatment with sialidase from Clostridium perfringens (Sigma) [39]. Asialofibrin films were prepared from 0.0075 -7.5 mg/ml asialofibrinogen solutions (40 pUwell) in NaCVP, by addition of 2 U/mg fibrinogen of bovine thrombin (Sigma, 2000 U/mg) and incubation for 1 h at 25°C.…”

Section: Quantitative Binding Studiesmentioning

confidence: 99%

Probing hydrogen‐bonding interactions of bovine heart galectin‐1 and methyl β‐lactoside by use of engineered ligands

Solı́s

Jiménez‐Barbero

Martín‐Lomas

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

The binding of different synthetic monodeoxy, 0-methyl and fluorodeoxy derivatives of methyl P-lactoside to galectin-1 from bovine heart has been studied to probe the role of hydrogen bonding in the recognition and binding. The energetic contributions of the hydroxyl groups of methyl ,8-lactoside directly involved in the interaction have been estimated and the nature of the protein residues involved has been predicted on the basis of the free energy data. Interpretations of the results have been sustained by molecular modeling of the three-dimensional structure of the sugars in solution. One side of the disaccharide molecule is not involved (HO-6 and HO-2') or only marginally involved (HO-3') in hydrogen bonding. Moreover, 0-methylation at these positions causes an enhancement of the binding, suggesting favourable interactions of the methyl groups which may come into contact with hydrophobic residues at the periphery of the combining site. Hydrogen-bonding interactions are almost exclusively restricted to the other side of the molecule : the C-4' and C-6' hydroxyl groups act as donors of the strongest hydrogen bonds to charged groups of the lectin, while the C-3 hydroxyl group participates in a strong hydrogen bond with a neutral group. The results also suggest that the N-acetyl NH group in N-acetyllactosamine, as well as the hydroxyl group at position C-2 in methyl /3-lactoside, are involved in a polar interaction with neutral groups of the combining site. This hydrogen-bonding pattern contrasts markedly with that previously reported for the two galactose-specific Ricinus communis lectins. The recognition of different epitopes of the same basic structure underlies the differences in the oligosaccharide-binding specificities of galectin-1 and the R. communis lectins.Bovine heart muscle contains a soluble 14-kDa lectin, recently named galectin-1 [l], which is a member of a family of metal-independent P-galactoside-binding lectins (galectins), widely distributed in animal tissues. Although a specific function of these lectins has not been unequivocally demonstrated, they have been suggested to be involved in cellular-recognition events such as differentiation, development and metastasis of malignant cells [2-41, via recognition of specific cellular glycoconjugates. The recent finding of homologous lectins in some of the most primitive multicellular animals such as sponge [5] and nematode [6], suggests that the galectin family existed at a very early stage in evolution [7] and, consequently, that these lectins might be involved in 'essential minimum' functions of multicellular animals. Their highly conserved carbohydrate-binding specificity reflects the biological importance of the recognition of P-galactoside-containing structures.In general, the specificity and affinity in the molecular recognition of carbohydrates by proteins is achieved mainly through hydrogen bonds, with added contributions from van der Waal's contacts and stacking interactions of aromatic residues with the hydrophobic patches of the sugar [8-...

show abstract

“…What impact might the loss Gal have on fibrinogen? First, it is well established that a decrease in the sialic acid content lessens the electrostatic repulsion between fibrin monomers during polymerisation [6] , [9] , [23] …”

Section: Discussionmentioning

confidence: 99%

Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications

Brennan

2015

BBA Clinical

View full text Add to dashboard Cite

BackgroundFibrinogen is an acute phase glycoprotein whose concentration increases in response to trauma. The newly synthesised protein is functionally enhanced and it is known that treatment with neuraminidase increases the rate of fibrin polymerisation. To explore this, we examined the differences between the oligosaccharide structures of quiescent and acute phase fibrinogen.MethodsA series of plasma samples was obtained from two individuals suffering an acute phase response. Fibrinogen chains were examined directly by ESI mass spectrometry before and after digestion with N-glycosidase F and β1,4 galactosidase.ResultsThe Bβ and γ chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the Bβ chain showed an additional decrease corresponding to a further loss of NAcGlc. Incubation with N-glycosidase F normalised all isoform masses to that of the quiescent naked protein, confirming the N-linked oligosaccharide as the source of heterogeneity. β1,4 galactosidase treatment showed the structural difference was the absence of the penultimate Gal from the biantennary oligosaccharides, and mapping of tryptic glycopeptides confirmed these results showing that approximately half the chains lacked Gal.Conclusions and implicationsThe failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge.

show abstract

Desialylation of fibrinogen with neuraminidase. Kinetic and clotting studies

Cited by 17 publications

References 11 publications

The effects of additional carbohydrate in the coiled‐coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aα Arg141→Ser with extra glycosylation)

The effects of additional carbohydrate in the coiled‐coil region of fibrinogen on polymerization and clot structure and properties: characterization of the homozygous and heterozygous forms of fibrinogen Lima (Aα Arg141→Ser with extra glycosylation)

Probing hydrogen‐bonding interactions of bovine heart galectin‐1 and methyl β‐lactoside by use of engineered ligands

Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications

Contact Info

Product

Resources

About