8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein.
8-oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) has been regarded simply as a oxidative mutagenic byproduct. The results obtained in this study imply that it may act as a down-regulator of respiratory burst of neutrophils. Human neutrophils treated with PMA produced superoxides and at the same time, the cytosol of these cells was intensely immunostained by 8-oxo-7,8-dihydroguanosine(8-oxoG) antibody, indicating that 8-oxoG-containing chemical species including 8-oxoGTP are produced. Human neutrophil lysates treated with PMA also produced superoxides, which was stimulated by GTPgammaS but inhibited by 8-oxoGTPgammaS. Moreover, 8-oxoGTPgammaS suppressed the stimulatory action of GTPgammaS. Likewise, GTPgammaS stimulated Rac activity in neutrophil lysates but 8-oxoGTPgammaS and GDP inhibited it. The inhibitory effect of GDP was one tenth that of 8-oxoGTPgammaS. Here again, 8-oxoGTPgammaS also suppressed the stimulatory action of GTPgammaS on Rac activity. These results imply the possibility that 8-oxoGTP is formed during respiratory burst of neutrophils and limits neutrophil production of superoxides by antagonizing GTP toward Rac.
Kim
Hee Joon
HJ
Department of Pharmacology, Eulji University School of Medicine, Daejeon, South Korea.
Yoon
Sun-Hee
SH
Ryu
Hyun-Ok
HO
Yoon
Byung-Hak
BH
Choi
Seongwon
S
Ye
Sang-Kyu
SK
Chung
Myung-Hee
MH
D000328:Adult; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D003848:Deoxyguanine Nucleotides / Q000276:immunology / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D002273:Carcinogens; D003848:Deoxyguanine Nucleotides; D013481:Superoxides; C078206:8-oxodeoxyguanosine triphosphate; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019255:NADPH Oxidases; D020744:rac GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate