Signaling Role of Reactive Oxygen Species in Platelets

Abstract

Review. Reactive oxygen species are formed as a result of redox reactions and are involved in signaling associated with cell growth, differentiation, and death. Platelets are both a source and a target of reactive oxygen species. The review regards the molecular mechanisms of the reactive oxygen species formation under platelet activation conditions and effects of altered redox balance on platelet function. The main platelet sources of reactive oxygen species are isoforms of NADPH oxidases, cyclooxygenase, xanthine oxidase, and mitochondrial electron transport chain. Reactive oxygen species produced during platelet activation by agonists act as secondary messengers and can interfere with signaling pathways that enhance agonist-induced platelet activation. The signaling pathway mediated by glycoprotein VI, the main platelet receptor for collagen, leading mainly to the generation of intracellular reactive oxygen species, as well as the signaling pathway activated by thrombin, leading to the production of extracellular reactive oxygen species are considered. Extracellular reactive oxygen species enhance initial signaling and support platelet recruitment and activation. Activated platelets are involved in the coupling of thrombosis, inflammation, and innate immune responses. The platelet antioxidant systems play an important role in preventing the cytotoxic effects of reactive oxygen species, as well as in the regulation of platelet signaling pathways. The authors of the review and other researchers have shown that the redox status of platelets can serve as a biomarker in the studies on prevention and treatment of diseases involving oxidative stress and can be used for objective assessments of the patients' condition severity (including depression and schizophrenia, in which the authors found a decrease in the activity of platelet glutathione -dependent antioxidant enzymes).