Ozone-induced damage of fibrinogen molecules: identification of oxidation sites by high-resolution mass spectrometry

Yurina, L. V.; Vasilyeva, A. D.; Indeykina, Maria I.; Бугрова, А. Е.; Biryukova, M. I.; Kononikhin, Alexey; Nikolaev, E. N.; Rosenfeld, M. A.

doi:10.1080/10715762.2019.1600686

Cited by 19 publications

(15 citation statements)

References 57 publications

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“…Indeed, markers of oxidative stress in plasma such as nitrotyrosine, soluble receptor for AGE, 8-iso-PGF2α, oxidized low-density lipoprotein, and total plasma carbonylation, have been correlated with plasma fibrin clot permeability [ 100 , 101 ]. However, none of the residues responsible for binding plasmin to fibrin or for cleavage by plasmin [ 102 ] have been subjected to ozone-induced oxidation [ 103 ], although some of the oxidized sites were near these crucial sites. In summary, current evidence shows that the diabetic milieu promotes fibrinogen modifications, particularly glycations, which are of paramount importance in the formation of abnormal fibrin clot structure.…”

Section: Mechanisms Of Hypofibrinolysis In T2dmmentioning

confidence: 99%

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Bryk-Wiązania

Undas

2021

Cardiovasc Diabetol

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A prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM). Apart from increased platelet reactivity, endothelial dysfunction, hyperfibrinogenemia, and hypofibrinolysis are observed in T2DM. A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported, indicating complex associations between platelet activation, fibrin formation and clot structure, and fibrinolysis inhibitors, in particular, elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity. Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM. Enhanced thrombin generation, a proinflammatory state, increased release of neutrophil extracellular traps, elevated complement C3, along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM. Antidiabetic agents such as metformin and insulin, as well as antithrombotic agents, including anticoagulants, have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM. Notably, recent evidence shows that hypofibrinolysis, assessed in plasma-based assays, has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients. This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients, with an emphasis on hypofibrinolysis and its impact on clinical outcomes. We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients.

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Section: Mechanisms Of Hypofibrinolysis In T2dmmentioning

confidence: 99%

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Bryk-Wiązania

Undas

2021

Cardiovasc Diabetol

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“…We found 253 positions of 307 PTMs, reported in 30 works [ 5 , 6 , 12 , 15 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] focusing on fibrinogen modified either in vivo or in vitro (see Figure 2 and Table S1 ). The positions of PTMs are reported according to the mature chains, i.e., sequences without a signal peptide.…”

Section: Resultsmentioning

confidence: 70%

“…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]. Both reports originate from the same group and use the same setup for their experiment.…”

Section: Discussionmentioning

confidence: 79%

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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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“…In the second step, the five most intensive peaks from the first stage were subjected to collision-induced dissociation (CID), and the fragment spectra were registered in a linear ion trap (the number of ions in LTQ was set to 3 × 10 4 ). After fragmentation, the corresponding parent masses were dynamically excluded from consideration for the next 30 s [ 30 ]. For each series of samples, as mentioned above, three biological replicates were carried out, for which measurements were done in triplicate to ensure that the obtained data were reliable and reproducible.…”

Section: Methodsmentioning

confidence: 99%

The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation

et al. 2020

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The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-mediated oxidation of the blood coagulation factor XIII (FXIII) at the different stages of its enzymatic activation is studied for the first time in this paper. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colorimetry demonstrate that in the process of FXIII’s conversion into FXIIIa, the vulnerability of FXIII to hypochlorite-induced oxidation increased as follows: native FXIII < FXIII + Ca2+ << FXIII + Ca2+/thrombin. The modification sites were detected among all the structural regions of the catalytic FXIII-A subunit, except for the activation peptide, and embraced several sushi domains of the FXIII-B subunit. Oxidized amino acid residues belonging to FXIII-A are surface-exposed residues and can perform an antioxidant role. The regulatory FXIII-B subunits additionally contribute to the antioxidant defense of the catalytic center of the FXIII-A subunits. Taken together, the present data along with the data from previous studies demonstrate that the FXIII proenzyme structure is adapted to oxidation.

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Ozone-induced damage of fibrinogen molecules: identification of oxidation sites by high-resolution mass spectrometry

Cited by 19 publications

References 57 publications

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

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

The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation

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