Hypochlorite-Induced Oxidative Modification of Fibrinogen

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

doi:10.1134/s1607672919010101

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…Only six amino acid residues modified by OCl − were found in both Yurina's [42] study and the present work, namely AαD477, BβP216, BβW293, γW76, γF226 (dioxidated), and γH340. Furthermore, Yurina et al [42] noticed BβD154 to be oxidized by OCl − . We found that BβD154 is modified by both, MDA and SIN-1, but not by NaOCl.…”

Section: Discussionsupporting

confidence: 60%

“…Similar PTM count was observed in Aα chain (26 by NaOCl, 8 by MDA, and 3 by SIN-1) and in γ chain (23 by NaOCl, 8 by MDA and 4 by SIN-1). In contrast, Yurina et al [42] and Nowak et al [37] found that higher amounts of PTMs induced by OCl − in the Aα chain of human fibrinogen than those in the Bβ and γ chains. This disagreement could be explained by a different technique for PTM detection (we use MS, Nowak et al use combination of gel electrophoresis and Western blot with anti-nitrotyrosine and anti-DNP antibodies).…”

Section: Discussionmentioning

confidence: 90%

“…Effect of oxidative stress on fibrinogen was extensively studied mainly on the mesoscopic scale. To the best of our knowledge, only few studies have been performed on more detailed level using either MS to identify the position and nature of the given PTMs (e.g., [35,42,43]) or MD ( [56,57]) to observe the early stages of fibrinogen structural alternations after the PTM induction. In this study, we combined MS and MD in order to describe the mechanism by which PTMs may influence the behavior of fibrinogen.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it was reported that methionines AαM476, BβM367, and γM78 are more prone to oxidation by HOCl than methionines BβM305, BβM190, and AαM91 [35]. Recently, Yurina et al [42] revealed that hypochlorite concentration of 500 μmol/mg fibrinogen, but not 50 μmol/mg fibrinogen, leads to fibrinogen fragmentation. Certain modifications induced in the fibrinogen structure by HOCl partly differed from those induced by ozone [43].…”

Section: Introductionmentioning

confidence: 99%

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Impact of posttranslational modifications on atomistic structure of fibrinogen

et al. 2020

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Oxidative stress in humans is related to various pathophysiological processes, which can manifest in numerous diseases including cancer, cardiovascular diseases, and Alzheimer's disease. On the atomistic level, oxidative stress causes posttranslational modifications, thus inducing structural and functional changes into the proteins structure. This study focuses on fibrinogen, a blood plasma protein that is frequently targeted by reagents causing posttranslational modifications in proteins. Fibrinogen was in vitro modified by three reagents, namely sodium hypochlorite, malondialdehyde, and 3-morpholinosydnonimine that mimic the oxidative stress in diseases. Newly induced posttranslational modifications were detected via mass spectrometry. Electron microscopy was used to visualize changes in the fibrin networks, which highlight the extent of disturbances in fibrinogen behavior after exposure to reagents. We used molecular dynamics simulations to observe the impact of selected posttranslational modifications on the fibrinogen structure at the atomistic level. In total, 154 posttranslational modifications were identified, 84 of them were in fibrinogen treated with hypochlorite, 51 resulted from a reaction of fibrinogen with malondialdehyde, and 19 were caused by 3-morpholinosydnonimine. Our data reveal that the stronger reagents induce more posttranslational modifications in the fibrinogen structure than the weaker ones, and they extensively alter the architecture of the fibrin network. Molecular dynamics simulations revealed that the effect of posttranslational modifications on fibrinogen secondary structure varies from negligible alternations to serious disruptions. Among the serious disruptions is the oxidation of γR375 resulting in the release of Ca 2+ ion that is necessary for appropriate fibrin fiber formation. Folding of amino acids γE72-γN77 into a short α-helix is a result of oxidation of γP76 to glutamic acid. The study describes behaviour of fibrinogen coiled-coil connecter in the vicinity of plasmin and hementin cleavage sites.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of posttranslational modifications on atomistic structure of fibrinogen

et al. 2020

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“…We found 253 positions of 307 PTMs, reported in 30 works [5,6,12,15, 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: Ptms Reported In Fibrinogenmentioning

confidence: 69%

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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