Potential role of adaptive response by cellular bioenergetic sensor of AMP-activated protein kinase in the implementation of the action of radioprotectors from alpha1-adrenergic agonists

Abstract

AMP-activated protein kinase as a universal metabolic sensor regulates the processes of anabolism and catabolism in the body. Activation of AMP-activated protein kinase occurs with a decrease in ATP content in the cell, which occurs under the influence of stress of various etiologies: with fasting, acute hypoxia, physical exertion, with radiation lesions and many other pathophysiological conditions of the body. The increase in its activity can be initiated pharmacologically through G-protein-coupled receptors, including ala1-adrenoagonists, exhibiting unique radioprotective properties on the example of indralin. AMP-activated protein kinase takes part through succinate dehydrogenase (respiratory chain complex II). in enhancing cellular respiration and ATP synthesis. According to the existing hypothesis, with excessive stimulation of AMP-activated protein kinase by alpha1-adrenoagonists, acute cellular hypoxemia develops, which is one of the main mechanisms for the implementation of their action. Under these conditions, the reduction of cell death from acute hypoxia with the stimulation of AMP-activated protein kinase and the participation of nitric monoxide is carried out by the transition to aerobic glycosis. The second important mechanism of protection by alpha1-agonists at large doses of radiation implements an anti-apoptic effect through the PPAR-AMPK-PGC-1α axis, maintaining the functional state of mitochondria. When stimulated with alpha1-adrenoagonists, sirtuin 1 provides an increase NAD+ in the cell, and through PGC-1α mitochondrial biogenesis is carried out, the required intensity of metabolism, cellular respiration and ATP synthesis. These processes may be facilitated by a closely related alpha-1-adrenoagonist cell cycle arrest associated with AMP-protein kinase, which favors affected DNA repair. The potential anti-apoptic properties of the alpha1-adrenoagonist igralin may contribute to the development of high radioprotective properties of the radriorotector at ultra-lethal doses of radiation.