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

• Published in: Free radical research 2009, Vol.43 (1), p.78-84
• Main Authors: Lee, Sun-Hye, Taek Han, Sang, Choi, Seong-Won, Sung, Seung-Yong, You, Ho-Jin, Ye, Sang-Kyu, Chung, Myung-Hee
• Format: Article
• Language: English
• Subjects: 8-oxo-deoxyguanosine; Animals; Cells, Cultured; chemotaxis; Chemotaxis - drug effects; cytokines; Deoxyadenosines - adverse effects; Deoxyadenosines - pharmacology; Drug Evaluation, Preclinical; Interferon-gamma - secretion; macrophage; Macrophages - drug effects; Macrophages - metabolism; Macrophages - physiology; Macrophages - secretion; Male; Mice; Mice, Inbred C57BL; NADPH Oxidases - metabolism; phagocytosis; Phagocytosis - drug effects; Rac; rac GTP-Binding Proteins - antagonists & inhibitors; rac GTP-Binding Proteins - metabolism; rac GTP-Binding Proteins - physiology; ROS; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760802609432

Rac is a protein involved in the various functions of macrophages (M ), including the production of reactive oxygen species (ROS), phagocytosis, chemotaxis and the secretion of cytokines (such as -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 M using mouse peritoneal M (MpM ). It is reported that 8-oxodG was able to effectively inhibit Rac and the Rac-associated functions of MpM . 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 M that are intimately related to various pathological processes.