The Effect of Hypochlorite-Induced Fibrinogen Oxidation on the Protein Structure, Fibrin Self-Assembly, and Fibrinolysis

Abstract

This article studies the structural-functional damage of fibrinogen (FG) treated with hypochlorous acid (HOCl) in the concentration range (10–100 µM). Using tandem mass spectronomy (the MS/MS method), 15 modified amino acid residues with a dose-dependent susceptibility to the oxidizing agent are detected. Using turbidity measurements and confocal laser scanning microscopy (CLSM), it is shown that FG oxidation by 25–100 µM HOCl leads to the formation of a denser fibrin gel, a delayed onset of polymerization, and a decrease in the slope of the polymerization curve, presumably due to the conformational changes in the protein. At lower a HOCl concentration (10 µM), at least six amino acid residues are substantially modified (9–29%), but functionally such modified protein was not distinguishable from the native one. The detected amino acid residues are assumed to be scavengers of the reactive oxygen species (ROS), which prevent the alteration of FG functions.