Redox-dependent mechanisms of regulation of breast epithelial cell proliferation

Resumo

Activation of free radical oxidation in various types of cells, including breast epithelial cells, can lead to damage to macromolecules, particularly proteins involved in regulation of proliferation and programmed cell death. The glutathione, glutaredoxin and thioredoxin systems play an essential role in maintaining intracellular redox homeostasis. In this regard, modulation of the redox status of cells by means of a blocker and a protector of SH-groups of proteins can be used as a model for studying the role of redox proteins and glutathione in regulation of cell proliferation during the development of various pathological processes. In this study the state of thioredoxin, glutaredoxin, glutathione systems and their role in the regulation of HBL-100 breast epithelial cell proliferation during modulation of the redox status by using N-ethylmaleimide (NEM) and 1,4-dithioerythritol (DTE) have been investigated. The modulation of the redox status of the breast epithelial cells by the blocker (NEM) and the protector (DTE) of thiol groups of proteins and peptides influenced the functional activity of glutathione-dependent enzymes, glutaredoxin, thioredoxin, and thioredoxin reductase by changing concentrations of GSH and GSSG. Modulation of the redox status of HBL-100 cells was accompanied by an increase in the number of cells in the S phase of the cell cycle and a decrease of cells in G₀/G₁ and G₂/M phases as compared with the intact cell culture. The proposed method for evaluating the proliferative activity of cells during modulation of their redox state can be used in the development of new therapeutic approaches for treatment of diseases accompanied by the development of oxidative stress.