Dataset Information

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

ABSTRACT:

Background

Fibrinogen 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.

Methods

A 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 ?1,4 galactosidase.

Results

The B? and ? chains of acute phase fibrinogen showed a mass decrease of 162 Da (Gal) in some 50% of the molecules, and the B? 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. ?1,4 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 implications

The 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.

SUBMITTER: Brennan SO

PROVIDER: S-EPMC4661561 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Brennan Stephen O SO

BBA clinical 20150304

<h4>Background</h4>Fibrinogen 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.<h4>Methods</h4>A series of plasma samples was obtained from two individuals suffering an acute phase response. ...[more]

PMID: 26675134

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Project description:It has been proved in experiments that there are at least five phases of solid hydrogen at high pressure, however, only the structure of phase I has been absolutely determined. We revisited the phase space of solid hydrogen in the pressure range of 200-500 GPa using the particle swarm optimization technique combined with first-principles simulations. A novel orthorhombic structure named Ama2 is proposed as a possible candidate structure for phase IV. The Ama2 structure is a 'mixed structure' with two different types of layers and is distinctly different from the previously reported Pc structure. Enthalpies and Gibbs free energies show that Ama2 and Pc are competitive in the pressure region of phase IV. Nevertheless, the Raman and infrared vibron frequencies of Ama2 calculated by using density functional perturbation theory based on first-principles lattice dynamics show a better agreement with the experimental measurements than those of the Pc structure. And the pressure dependence of these low-frequency Raman vibrons of Ama2 obtained from the first-principles molecular dynamics simulation shows a steeper slope, which resolves the long-standing issue of large discrepancies between the calculated Raman frequencies and the experimental ν 1 [P. Loubeyre, F. Occelli and P. Dumas, Phys. Rev. B: Condens. Matter Mater. Phys., 2013, 87, 134101 and C. S. Zha, R. E. Cohen, H. K. Mao and R. J. Hemley, Proc. Natl. Acad. Sci. U.S.A., 2014, 111, 4792]. Structural and vibrational analyses show that the hydrogen molecules in the weakly bonded molecular layer of Ama2 form distorted hexagonal patterns, and their vibration can be used to explain the experimental ν 1 vibron. It is found that the weakly bonded layer is almost the same as the layers in the C2/c structure. This confirms the experimental conclusion [P. Loubeyre, F. Occelli and P. Dumas, Phys. Rev. B: Condens. Matter Mater. Phys., 2013, 87, 134101] that the ordering of hydrogen molecules in the weakly bonded molecular layers of the 'mixed structure' for phase IV is similar to that in the layers of the C2/c structure.

Dataset Information

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

Background

Methods

Results

Conclusions and implications

Publications

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

Similar Datasets

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