Andriichuk T. The biochemical mechanisms of the radiation-induced apoptosis

The stages of radiation-induced apoptosis, namely the nuclear-mediated, mitochondrial and receptor-dependent pathways, have been studied. The action of ionizing radiation, both directly through structural damage of nucleoprotein complexes, and due to the imbalance between expression of anti- and proapoptotic genes led to activation of the nuclear path of apoptosis. Radiation-induced changes in the mitochondrial compartment were established, in particular, the disturbance of electron transport chain and release of proapoptotic factors from the intermembrane space, which was mediated by Bax protein. Fas (as part of the DISC-complex) level has been measured to assess the contribution of receptor pathway to apoptosis upon radiation exposure. The established changes of functioning of the main classes of cysteine proteases - caspases (2, 3, 6, 8, 9), calpains, and lysosomal cathepsin B indicated a significant and specific contribution of the proteolysis system to radiation-induced apoptosis. Our results indicated the significant disorders of pro-antioxidative homeostasis upon radiation exposure. Redox-regulation of the components of nuclear, receptor-dependent, mitochondrial, and lysosomal-mediated signaling cascades determined their involvement in radiation-induced apoptosis, postulating oxidative stress as key mediator of apoptosis. The violation of the energy state, which is accompanied by changes in ATP level due to the activation of purine catabolism, has been revealed. Flow cytometric analysis was used to concern the induction of apoptosis after X-ray exposure and our results showed increased apoptosis (in a dose-dependent manner). So according to our investigations we propose the complex view on molecular architecture (the molecules and pathways) and essential biochemical processes special for radiation-induced apoptosis.