Inhibition of Rac and Rac-linked functions by 8-oxo-2′-deoxyguanosine in murine macrophages

Abstract

Rac is a protein involved in the various functions of macrophages (Mphi), including the production of reactive oxygen species (ROS), phagocytosis, chemotaxis and the secretion of cytokines (such as gamma-INF). This study tested the effects of nucleosides containing 8-oxoguanine(8-hydroxyguanine) such as 8-oxo-2'-guanosine (8-oxoG) or 8-oxo-2'-deoxyguanosine (8-oxodG), on Rac and the above-listed Rac-associated functions of Mphi using mouse peritoneal Mphi (MpMphi). It is reported that 8-oxodG was able to effectively inhibit Rac and the Rac-associated functions of MpMphi. Compared to 8-oxodG, 8-oxoG showed negligible effects. Furthermore, normal nucleosides such as deoxyguanosine (dG), guanosine (G) and adenosine (A) did not exert any effects. These results suggest that 8-oxodG could be used as a potential tool to modulate the functions of Mphi that are intimately related to various pathological processes.