The effect of hypochlorite- and peroxide-induced oxidation of plasminogen on damage to the structure and biological activity

• Published in: International journal of biological macromolecules 2022-05, Vol.206, p.64-73
• Main Authors: Vasilyeva, Alexandra, Yurina, Lyubov, Ivanov, Vladislav, Azarova, Daniela, Gavrilina, Elizaveta, Indeykina, Maria, Bugrova, Anna, Kononikhin, Alexey, Nikolaev, Evgene, Rosenfeld, Mark
• Format: Article
• Language: English
• Subjects: Antioxidant methionines; Dynamic light scattering; Electrophoresis; Fibrinolysin; High-resolution mass spectrometry; Hydrogen Peroxide; Hypochlorous Acid - chemistry; Oxidation; Peroxides; Plasmin; Plasminogen; Plasminogen - chemistry; Primary structure; Tandem Mass Spectrometry
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.02.128

In this study, we examined for the first time the effect of the HOCl/OCl−- and H2O2-induced oxidation of Glu-plasminogen on damage to its primary structure and the biological activity of plasmin. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colourimetry, demonstrated that none of the oxidised amino acid residues found in the proenzyme treated with 25 μM HOCl/OCl− or 100 μM H2O2 were functionally significant for plasminogen. However, the treatment of plasminogen with increasing concentrations of HOCl/OCl− from 25 μM to 100 μM or H2O2 from 100 μM to 300 μM promoted a partial loss in the activity of oxidised plasmin. Several methionine residues (Met57, Met182, Met385, Met404, Met585, and Met788) localized in different protein domains have been shown to serve as ROS traps, thus providing an efficient defense mechanism against oxidative stress. Oxidised Trp235, Trp417, Trp427, Trp761, and Tyr672 are most likely responsible for the reduced biological activity of Glu-plasminogen subjected to strong oxidation. The results of the present study, along with those of previous studies, indicate that the structure of Glu-plasminogen is adapted to oxidation to withstand oxidative stress induced by ROS. [Display omitted] •Plasminogen treatment with HOCl/OCl− or H2O2 caused damage of all domains.•A number of Met residues in the plasminogen structure serve as ROS scavengers.•Oxidation of some Trp and Tyr residues induced reduced activity of plasminogen.•The structure of Glu-plasminogen is adapted to oxidation.