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8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein
Cited 14 time in
Web of Science
Cited 14 time in Scopus
- Authors
- Issue Date
- 2007-05-23
- Publisher
- Taylor & Francis
- Citation
- Free Radic Res. 2007 Jun;41(6):655-62.
- Keywords
- Adult ; Carcinogens/pharmacology ; Cells, Cultured ; Deoxyguanine Nucleotides/immunology/*pharmacology ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Diphosphate/metabolism ; Humans ; NADPH Oxidase/metabolism ; Neutrophils/*drug effects/metabolism ; Respiratory Burst/*drug effects ; Superoxides/*metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; rac GTP-Binding Proteins/*metabolism
- 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.
- ISSN
- 1071-5762 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17516238
https://hdl.handle.net/10371/27862
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