title: 8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein.
abstract: 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.
authors.affiliation: Department of Pharmacology, Eulji University School of Medicine, Daejeon, South Korea.
authors.forename: Hee Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Hyun-Ok
authors.initials: HO
authors.lastname: Ryu
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Yoon
authors.forename: Seongwon
authors.initials: S
authors.lastname: Choi
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Chung
mesh_terms: 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*
chemical_list: 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