Mechanotransduction signaling pathways of erythrocytes associated with restructuring of cell metabolism

Abstract

Erythrocytes exhibit the properties of "sensor" of mechanical tension, hypoxia and "regulator" of vascular tone. In the in vivo bloodstream, these cells are constantly exposed to flow during which they experience varying levels of shear stress and strain. In this regard, these cells have well-established signaling mechanisms, with the participation of which a chemical response to a stress factor is formed. Vibration is a factor that, depending on its own physical characteristics, combines mechanical influence with an oxidative state or hypoxia. Thus, it was of interest to investigate how erythrocytes use certain signaling pathways to maintain metabolic homeostasis under the influence of low-frequency vibration. The paper examines the effect of vibration (frequency range 8–32 Hz, amplitudes 0.50 ± 0.04 and 0.90 ± 0.08 mm) on the energy state of human erythrocytes in the absence of glucose. In this connection, the changes of intracellular ATP, 2,3-BPG and inorganic phosphate (Pi) in human erythrocytes during 3-hour vibration exposure were investigated. The activity of Na+,K+-ATPase was investigated as an indicator reflecting cellular needs for ATP. Cytosolic 5’-nucleotidase (cN-1A) and AMP-deaminase (AMPDA) activities were investigated as indicators of the level of catabolism of purine nucleotides. To assess the involvement of adenosine in the processes of reverse signaling through the ADORA2B – AMPK BPGM axis, the activity of ectonucleotidase (eN) was investigated. Based on the obtained experimental data, an analysis of the signal mechanisms involved in the mechanotransduction of the vibration effect was carried out. It is shown that under certain conditions of vibration exposure (frequency interval 20–32 Hz, A = 0.50 ± 0.04 mm and 12–32 Hz, A = 0.90 ± 0.08 mm) erythrocytes use signaling and metabolic pathways aimed at increasing the content of ATP, 2,3-BPG and restoration of the energy charge of cells. One of these pathways is controlled by AMP-kinase (AMPK), which in turn is a participant in the signaling cascade that begins with adenosine receptors ADORA2B. AMPK turns off consumption pathways and turns on alternative pathways for ATP regeneration and activation of 2,3-BPG formation mechanisms. These ways are aimed at overcoming the state of hypoxia. Experimental data on the participation of AMP catabolism enzymes in ATP recovery processes were analyzed.

Keywords

• atp, 2,3-bpg; na ,k -atpase; 5’-nucleotidase; амр-deaminase; hypoxia; adenylate metabolism; signaling mechanisms.