Damage of cystatin due to ROS-generation and radical-scavenging activity of antioxidants and associated compounds

Cystatins are thiol proteinase inhibitors present ubiquitously in mammalian system. They prevent unwanted proteolysis and are involved in several neurodegenerative diseases. Hydrogen peroxide, hydroxyl radical and superoxide radical were produced during the autoxidation of various cytotoxic agents namely 6-hydroxydopamine, 6-aminodopamine, 6,7-dihydroxytryptamine, and dialuric acid. Reactive oxygen species (ROS) such as singlet oxygen [O-2(-)] and hydroxyl radicals result in nonspecific reactivity, thus involved in several pathological conditions such as inflammation and reperfusion injury leading to damage of different biological molecules due to the production of enzyme myeloperoxidase because of activation of neutrophils in these diseases. As Myeloperoxidase [MPO] is released extracellularly by activated monocytes and is highly basic protein that damages the localized sites. The onset and progression of several diseases is a complex process in which oxidation is believed to play significant role. Oxidized lipids and proteins that are detected in early, intermediate and advanced stage of human neurodegenerative diseases (plaques) have revealed considerably elevated levels of reactive oxygen species showing their involvement in brain diseases. In the present study, it has been demonstrated that H2O2 induced modifications in brain cystatin leads to its inactivation and degradation. It was also found that the damage from the oxidants occurred mainly because of the (ROS) hydroxyl radicals [OH center dot]produced by H2O2 which in turn changes the conformation of the Cystatin, a major factor for the damage of this significant protein. It is one of the cause of protease-antiprotease imbalance in mammals leading to progression of several diseases. (C) 2018 Elsevier B.V. All rights reserved.