Inhibition of Rac and Rac-linked functions by 8-oxo-2'-deoxyguanosine in murine macrophages.
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.
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
Sun-Hye
SH
Lee
Sang
S
Taek Han
Seong-Won
SW
Choi
Seung-Yong
SY
Sung
Ho-Jin
HJ
You
Sang-Kyu
SK
Ye
Myung-Hee
MH
Chung
D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003839:Deoxyadenosines / Q000009:adverse effects / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*
D003839:Deoxyadenosines; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D007371:Interferon-gamma; D019255:NADPH Oxidases; D020744:rac GTP-Binding Proteins