Regulation of redox processes in biological systems with the participation of the Keap1/Nrf2/ARE signaling pathway, biogenic selenium nanoparticles as Nrf2 activators

Abstract

The article is devoted to the mechanisms of regulation of redox processes in cells, a review of the Keap1 / Nrf2 / ARE redox-sensitive signaling system as a fundamental pathway that plays a key role in maintaining cellular redox homeostasis under stressful, inflammatory, carcinogenic and proapoptotic conditions. The structure of the cysteine-rich repressor protein Keap1, which is responsible for sensory perception of electrophiles and reactive oxygen species, the structure and functions of the transcription factor Nrf2, mechanisms of Nrf2 activation through the Keap1 / Nrf2 / ARE signaling system, which regulates the transcription and expression of cellular cytoprotective and antioxidant proteins, are described. Published data on the specificity of the interaction of the components of this cellular signaling pathway, the mechanisms of Keap1 dependent and independent adaptive response to the action of inductors, the role of biogenic selenium nanoparticles synthesized by green chemistry with the participation of bacteria in these processes are analyzed; features of Nrf2 induction depending on the type of bacteria and the stabilizing shell. It has been shown that biogenic selenium nanoparticles (BNSe), synthesized by different types of bacteria, activate the transcription factor Nrf2 using the Keap1-independent activation pathway through mitogen-protein kinases (MAPK): p38, ERK1 / 2 and AKT-mediated phosphorylation of Nrf2, protect the intestinal epithelial barrier function from the effects of oxidative damage, normalize mitochondrial function. A detailed understanding of thiol-dependent and independent redox signaling mechanisms under physiological and pathological conditions will lead to a deeper understanding of the redox component in human and animal diseases. The use of biogenic nanoselen, synthesized with the participation of various bacterial species, has been demonstrated to activate the Keap1 / Nrf2 / ARE signaling pathway, which may be of practical interest as a therapeutic target for many redox-mediated diseases.

Keywords

• redox processes; reactive oxygen species; nanotechnology; “green chemistry”; biogenic nanoselen; cytoprotective proteins; antioxidant proteins