Post-Translational Oxidative Modifications of Hemostasis Proteins: Structure, Function, and Regulation.

Reactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins.

Electrospinning of biomimetic materials with fibrinogen for effective early-stage wound healing.

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.

Antioxidant role of methionine-containing intra- and extracellular proteins.

Significant evidence suggests that reversible oxidation of methionine residues provides a mechanism capable of scavenging reactive species, thus creating a cycle with catalytic efficiency to counteract or mitigate deleterious effects of ROS on other functionally important amino acid residues. Because of the absence of MSRs in the blood plasma, oxidation of methionines in extracellular proteins is effectively irreversible and, therefore, the ability of methionines to serve as interceptors of oxidant molecules without impairment of the structure and function of plasma proteins is still debatable. This review presents data on the oxidative modification of both intracellular and extracellular proteins that differ drastically in their spatial structures and functions indicating that the proteins contain antioxidant methionines/the oxidation of which does not affect (or has a minor effect) on their functional properties.

Hypochlorite-induced oxidation of fibrinogen: Effects on its thermal denaturation and fibrin structure.

Background: Human fibrinogen, which plays a key role in plasma haemostasis, is a highly vulnerable target for oxidants. Fibrinogen undergoes posttranslational modifications that can potentially disrupt protein structure and function.

Methods: For the first time, by differential scanning calorimetry, dynamic and elastic light scattering and confocal laser scanning microscopy, the consequences of HOCl/OCl-induced oxidation of fibrinogen on its thermal denaturation, molecular size distribution and fibrin clot network have been explored.

Binding of Coagulation Factor XIII Zymogen to Activated Platelet Subpopulations: Roles of Integrin αIIbβ3 and Fibrinogen.

Factor XIIIa (fXIIIa) is a transglutaminase that plays a crucial role in fibrin clot stabilization and regulation of fibrinolysis. It is known to bind to procoagulant platelets. In contrast, the zymogen fXIII interaction with platelets is not well characterized.

Oxidation of proteins: is it a programmed process?

Proteins represent extremely susceptible targets for oxidants. Oxidative modifications of proteins may bring about violation of their structure and functionality. It implies that the structures of proteins are not infallible in terms of their antioxidant defence.

Fibrin self-assembly is adapted to oxidation.

Fibrinogen is extremely susceptible to attack by reactive oxygen species (ROS). Having been suffered an oxidative modification, the fibrinogen molecules, now with altered spatial structure and function of fibrin network, affect hemostasis differently. However, the potential effects of the oxidative stress on the early stages of the fibrin self-assembly process remain unexplored.

Covalent structure of single-stranded fibrin oligomers cross-linked by FXIIIa.

FXIIIa-mediated isopeptide γ-γ bonds are produced between γ polypeptide chains of adjacent monomeric fibrin. Despite the use of the different methodological approaches there are apparently conflicting ideas regarding the orientation of γ-γ bonds. To identify the orientation of these bonds a novel approach has been applied.

Ozone-induced oxidative modification of fibrinogen: role of the D regions.

Native fibrinogen is a key blood plasma protein whose main function is to maintain hemostasis by virtue of producing cross-linked fibrin clots under the influence of thrombin and fibrin-stabilizing factor (FXIIIa). The aim of this study was to investigate mechanisms of impairment of both the molecular structure and the spatial organization of fibrinogen under ozone-induced oxidation. FTIR analysis showed that ozone treatment of the whole fibrinogen molecule results in the growth of hydroxyl, carbonyl, and carboxyl group content.

Ozone-induced oxidative modification of plasma fibrin-stabilizing factor.

The plasma fibrin-stabilizing factor (pFXIII) function is to maintain a hemostasis by the fibrin clot stabilization. The conversion of pFXIII to the active form of the enzyme (FXIIIа) is a multistage process. Ozone-induced oxidation of pFXIII has been investigated at different stages of its enzyme activation.