Ozone-induced oxidative modification of fibrinogen: Role of the D regions

Rosenfeld, M. A.; Щеголихин, А. Н.; Bychkova, A. V.; Leonova, V. B.; Biryukova, M. I.; Kostanova, E. A.

doi:10.1016/j.freeradbiomed.2014.08.018

Cited by 25 publications

(7 citation statements)

References 60 publications

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“…Oxidative stress has been widely implicated in physiological processes such as aging, in various disease pathogenesis, including arterial and venous thrombosis. Proteins are major targets for oxidants, and fibrinogen is a common target for oxidative post-translational modifications (Martinez et al 2013; Rosenfeld et al 2014). Neutrophils and monocytes, the most prevalent leukocytes in the sites of inflammation and venous thrombi, generate nitrating metabolic intermediates capable of nitration of fibrinogen (Heffron et al 2009; Martinez et al 2012).…”

Section: 4 Variations and Modulation Of Fibrin(ogen) Structure Andmentioning

confidence: 99%

Fibrin Formation, Structure and Properties

Weisel

Litvinov

2017

Subcellular Biochemistry

554

498

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Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin.

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Section: 4 Variations and Modulation Of Fibrin(ogen) Structure Andmentioning

confidence: 99%

Fibrin Formation, Structure and Properties

Weisel

Litvinov

2017

Subcellular Biochemistry

554

498

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“…The oxidation of γP70 to glutamic semialdehyde, among other PTMs, was reported in fibrinogen that was oxidized in vitro by O 3 [ 29 ]. No effect of oxidation on fibrinogen properties is described in the cited paper, but it can be found in the paper by Rosenfeld et al [ 13 ]. It is questionable whether γP(Ox)70 is present in the samples characterized by the latter work, as it is not reported in a paper by Yurina et al [ 30 ] which extends the work of Bychkova et al [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…An increased concentration of the oxidizing agent increases levels of γM78 oxidation. The O 3 oxidation of fibrinogen decreases the content of α-helices in protein [ 13 ]. The oxidation by H 2 O 2 decreases fibrin cross-linking and the stiffness of the clot [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, the oxidation of fibrinogen decreases its polymerization rate, clot lysis, maximum turbidity, the diameter of fibrin fibers, the stiffness of the clot, and its permeability. On a microscale level, oxidation decreases the content of α-helices in the fibrinogen structure and of CH 2 and CH 3 moieties, and increases the content of carbonyl groups in sidechains [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Dynamic Simulations Suggest That Metabolite-Induced Post-Translational Modifications Alter the Behavior of the Fibrinogen Coiled-Coil Domain

2021

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Fibrinogen is an abundant blood plasma protein that, inter alia, participates in blood coagulation. It polymerizes to form a fibrin clot that is among the major components of the thrombus. Fibrinogen reactions with various reactive metabolites may induce post-translational modifications (PTMs) into the protein structure that affect the architecture and properties of fibrin clots. We reviewed the previous literature to find the positions of PTMs of fibrinogen. For 7 out of 307 reported PTMs, we used molecular dynamics simulations to characterize their effect on the behavior of the fibrinogen coiled-coil domain. Interactions of the γ-coil with adjacent chains give rise to π-helices in Aα and Bβ chains of even unmodified fibrinogen. The examined PTMs suppress fluctuations of the γ-coil, which may affect the fibrinolysis and stiffness of the fibrin fibers. Citrullination of AαR104 and oxidations of γP70 and γP76 to glutamic semialdehyde unfold the α-helical structure of Aα and Bβ chains. Oxidation of γM78 to methionine sulfoxide induces the formation of an α-helix in the γ-coil region. Our findings suggest that certain PTMs alter the protein secondary structure. Thus, the altered protein structure may indicate the presence of PTMs in the molecule and consequently of certain metabolites within the system.

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“…The presence of covalent cross links between the polypeptide chains of the sta bilized polymeric fibrin was determined by electro phoresis of reduced samples. The functional groups of different samples of the cellular fibrin stabilizing factor were studied with a 6700 Nexus FTIR spectrometer (Thermo Nicolet, United States) equipped with a DTGS detector, as was described in detail previously [11]. The FTIR spectra were recorded in transmission mode at room temper ature in the 4000-400 cm -1 range at 4 cm -1 resolution digital interferogram resolution by averaging 64-128 accumulated scans.…”

mentioning

confidence: 99%

The oxidative modification of cellular fibrin-stabilizing factor

Rosenfeld

Щеголихин

Leonova

et al. 2016

Dokl Biochem Biophys

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For the first time, the induced oxidative modification of cellular fibrin-stabilizing factor (cFXIII) has been studied. According to the electrophoresis analysis, the conversion of oxidized cFXIII into FXIIIa resulted in producing the enzyme that significantly lost the initial enzymatic activity. At the same time, FXIIIa subjected to induced oxidation was completely devoid of enzymatic activity. The results of FTIR spectroscopy showed that the oxidation of cFXIII or FXIIIa was accompanied by profound changes both in chemical and spatial structures of the protein. The results of this study are in good agreement with our earlier assumption regarding the antioxidant role of the regulatory subunits B of plasma fibrin-stabilizing factor.

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Ozone-induced oxidative modification of fibrinogen: Role of the D regions

Cited by 25 publications

References 60 publications

Fibrin Formation, Structure and Properties

Fibrin Formation, Structure and Properties

Molecular Dynamic Simulations Suggest That Metabolite-Induced Post-Translational Modifications Alter the Behavior of the Fibrinogen Coiled-Coil Domain

The oxidative modification of cellular fibrin-stabilizing factor

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