The dynamics of actin filament polymerization in activated leukocytes under experimental diabetes mellitus against the background of agmatine administration

Abstract

To research the impact of agmatine on the redistribution of actin fractions, which are represented by cytoskeletal actin filaments, short actin filaments of the plasma membrane skeleton and actin monomers (G-actin) in rat leukocytes under experimental diabetes mellitus (EDM). Methods. Leukocytes were lyzed in Triton X-100 and subjected to centrifugation to obtain cytoskeletal actin filaments, short actin filaments and actin monomers, which were separated in SDS-PAАG, followed by the immunoblot analysis of anti-actin antibodies. Results. Under EDM, an intensification of the process of short actin filament depolymerization and an increase in the G-actin content were observed in leukocytes activated by sialospecific wheat germ lectin (WGA). Against a background of agmatine administration, the response dynamics to the WGA-stimulating effect was characterized by an increase in actin polymerization in the fraction of cytoskeletal filaments already after 0.5 min exposure to lectin, an exceptionally rapid depolymerization process after 1 min of the lectin treatment, and return to the initial indices after 3 min exposure to lectin. Conclusions. In leukocytes of animals with EDM against a background of agmatine administration, the transduction of WGA-induced signal through sialoglycoconjugates causes the actin redistribution. It indicates that this polyamine helps to restore and maintain a functional response of leukocytes to the activation signals.K e y w o r d s: actin, leukocytes, agmatine, experimental diabetes mellitus.

Agmatine prevents oxidative-nitrative stress in blood leukocytes under streptozotocin-induced diabetes mellitus

“…This facilitates the recovery of a balance between processes of actin polymerization and depolymerization in leukocytes ( Figure 5 ). A previously described increase in polymerized actin content in the fraction of cytoskeletal filament in leukocytes from animals with DM confirmed this effect [ 22 , 88 ].…”

“…The intracellular increase of ROS and RNS concentrations enhance the probability of Cys374 and Met44 residues oxidation in F-actin molecules. This leads to F-actin cytoskeleton destruction, thereby breaking the locomotive and protective function of leukocytes [ 22 , 24 , 25 , 88 ]. The production of highly permeable reactive species also causes leakage of these molecules from the phagosomal membrane and deleterious effects on adjacent endothelial cells.…”

“…Furthermore, the increased levels of cellular reactive species also triggers or enhances programmed cell death [ 90 ]. This indicates that an imbalance between continuously produced ROS and RNS and deactivation of these molecules is critical for the maintainence of homeostasis and normal functioning of cell [ 88 , 89 , 90 ].…”