Exploring New Pathways of Advanced Oxidation Protein Products Formation: The Role of Hypochlorous Acid and Potassium Cyanate in Protein Modification

Advanced oxidation protein products (AOPP) are generated from oxidation that is mainly promoted by the action of hypochlorous acid (HOCl) on proteins, such as albumin. However, new pathways and targets associated with AOPP formation must be identified and thoroughly evaluated. Non-enzymatic post-translational modifications (NEPTMs), such as protein carbamylation, are relevant in chronic kidney disease and other inflammation-related processes. Therefore, the aim of this study was to determine whether incubating HOCl with gamma globulins promotes AOPP formation and whether potassium cyanate (KOCN)-induced carbamylation of albumin and gamma globulins is a new pathway for AOPP formation. Solutions comprising 451 and 86 μM of albumin and gamma globulins, respectively, were incubated with HOCl (2 and 4 mM) and KOCN (150 nM and 150 μM) for 30 min, and then AOPP formation and the concentrations of protein carbonyl and homocitrulline were monitored. Notably, HOCl-induced oxidation of gamma globulins and albumin increased AOPP production. Gamma globulins also generated a higher amount of AOPP than albumin. Exposure of albumin and gamma globulins to HOCl resulted in a significant increase in protein carbonyl content, whereas exposure to KOCN led to a significant increase in homocitrulline. These findings suggest that gamma globulins are a new target of AOPP and KOCN participates in an alternate pathway of AOPP formation, thereby providing a new hypothesis regarding the pathways of AOPP formation during inflammation.