THE EFFECT OF IONIZING RADIATION ON HIPPOCAMPAL NA,K-ATPASE ACTIVITY

Abstract

Ionizing radiation (IR) exposure initiates the rapid generation of reactive oxygen species (ROS), leading to oxidative stress and cellular damage. While ROS serve as critical signaling molecules under physiological conditions, excessive levels can disrupt membrane integrity via lipid peroxidation and impair membrane-bound enzymes such as Na⁺,K⁺-ATPase. In this context, our study investigates the dual effect of IR-induced ROS and endogenous ouabain on Na⁺,K⁺-ATPase activity. We demonstrate that different doses of IR (1 Gy and 5 Gy) initially enhance enzyme activity through reversible redox modification of thiol groups of the Na⁺,K⁺-ATPase complex. Simultaneously, IR stimulates the release of endogenous ouabain, which not only binds to Na⁺,K⁺-ATPase but also activates intracellular signaling cascades that further augment mitochondrial ROS production. This positive feedback loop—termed the “Na⁺,K⁺-ATPase oxidant amplification loop”—ultimately leads to irreversible oxidative modifications and enzyme inhibition under sustained oxidative stress. These findings highlight a redox-dependent biphasic regulation of Na⁺,K⁺-ATPase in response to IR, implicating both reversible and irreversible oxidative mechanisms in radiation-induced cellular effects.