Role of oxidative modification of proteins in the regulation and realization of cell death of blood lymphocytes under the conditions of blocking glutathione synthesis under oxidative stress

Abstract

Lymphocytes are key cells in inflammation. The realization of inflammation accompanied by the development of oxidative stress depends on metabolic processes occurring in blood lymphocytes. Experimental studies of molecular control of the redox status and apoptotic death of blood lymphocytes are relevant to study the role of lymphocytes in the pathogenesis of inflammation. The glutathione system plays a leading role in maintaining the redox status and oxidative modification of blood lymphocyte proteins. The study of molecular mechanisms of oxidative modification of proteins under the conditions of blocking glutathione synthesis is the basis for the targeting control of lymphocyte apoptosis. Inhibitory analysis is a molecular approach in experimental science used to study cellular metabolism by targeting specific stages of biochemical processes. The aim of the research was to determine the role of oxidative protein modification in redox regulation and cell death of blood lymphocytes when glutathione synthesis is inhibited during oxidative stress. The effect of exposure to the de novo glutathione synthesis inhibitor buthionine sulfoximine at a final concentration of 1 mM on the state of the glutathione system was studied in the experiment: content of reduced and oxidized glutathione, activity of glutathione reductase and glutathione peroxidase; on oxidative stress parameters: concentration of hydroxyl radical, reactive oxygen species, free SH-groups of proteins; on reversible and irreversible oxidative modification of proteins: content of glutathione bound to proteins, carbonyl derivatives of proteins, oxidized tryptophan and bityrosine; on realization and regulation of apoptotic death type: the number of annexin V+ cells and caspase-3 activity in blood lymphocytes. Blocking of de novo glutathione synthesis in blood lymphocytes was accompanied by the formation of oxidative stress, imbalance of glutathione system, changes in oxidative modification of proteins associated with the activation of apoptosis realization and completion. The obtained results indicate the participation of glutathione system components in reversible and irreversible oxidative modification of proteins, redox regulation and realization of apoptosis of blood lymphocytes. Therefore, modifying redox homeostasis through glutathionylation and carbonylation of cell proteins is a personalized apoptosis control mechanism.