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

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.

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.

Within a wide range of HOCl/^-OCl concentrations (50-300 μM), the molecular size distribution remained unimodal; however, the average size of the hydrated molecules decreased. HOCl/^-OCl-induced oxidation of fibrinogen resulted in the diminished thermal stability of regions D and E. As evidenced by elastic light scattering and confocal laser scanning microscopy, HOCl/^-OCl caused the formation of abnormal fibrin with a decreased diameter of individual fibres.

The current results along with data from previous studies enable one to conclude that the effect of HOCl/^-OCl-mediated oxidation on the thermal stability of region D is influenced directly by oxidative damage to the D region structure. Since the E region is not subjected to oxidative modification, its structural damage is likely to be mediated by the oxidation of other protein structures, in particular α-helical coiled-coils.

The experimental findings acquired in the current study could help to elucidate the consequences of oxidative stress in vivo on damage to the structure of fibrinogen/fibrin under the action of different ROS species.