Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure

Abstract

High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low proliferative rate of cardiac myocytes, research has looked at the effect of radiation on endothelial cells and consequent coronary heart disease as the mechanism of ratdiation induced cardiotoxicity. In fact, little is known concerning the direct effect of radiation on mitochondria dynamis in cardiomyocyte. The main effect of ionizing radiation is the production of ROS and recent works have uncovered that they directly participates to pivotal cell function like mitochondrial quality control. In particular ROS seems to act as check point within the cell to promote either mitochondrial biogenesis and survival or mitochondrial damage and apoptosis. Thus, it appears evident that the functional state of the cell, as well as the expression patterns of molecules involved in mitochondrial metabolism may differently modulate mitochondrial fate in response to radiation induced ROS responses. Different molecules have been described to localize to mitochondria and regulate ROS production in response to stress, in particular GRK2. In this review we will discuss the evidences on the cardiac toxicity induced by X ray radiation on cardiomyocytes with emphasis on the role played by mitochondria dynamism.

Keywords: Reactive Oxygen species; ionizing radiations, Mitochondria; signal transduction.

Figure 1:

In response to stress a part of mitochondria loss its mitochondrial potential membranes and Drp-1 induces (mitochondrial fission), consequentially PINK-1 is exposes on mitochondria damage and it drives mitochondria degradation trough phosphorilation of ubiquitination and activation of ubiquitine ligase Parkin (autophagosome digestion). The mitochondria has not lost its membrane potential activates the mitochondrial fusion through mitofusin 1, mitofusin 2 and Opa-1 with other part of mitochondria that has preserved its mitochondria potential membrane to form a new functional mitochondria (Mitochondria fusion).

Fig 2:

X-Ray cellular effects mediated by ROS. X –rays on plasma membrane induce an increase of ROS through activation of NOX1 and (5’ lipossigenase). X-ray can target to mitochondria bothe directly and indirectly: through increased ROS production: 1) the compounds of respiratory chain. 2) mtDNA generating trough mutation and deletion defective proteins to respiratory chain. 3) Alteration of redox signaling and mitochondrial dysfunctions that induces necrosis and apoptotic events. 4) Release of Cytocrome C outer mitochondria membranes into cytosolic fractions and formation of mPTP channel to induce respectively apoptotic and necrosis events.