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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 12 time in Web of Science Cited 12 time in Scopus
Authors
Kim, Hee Joon; Yoon, Sun-Hee; Ryu, Hyun-Ok; Yoon, Byung-Hak; Choi, Seongwon; Ye, Sang-Kyu; Chung, Myung-Hee
Issue Date
2007-05-23
Publisher
Taylor & Francis
Citation
Free Radic Res. 2007 Jun;41(6):655-62.
Keywords
AdultCarcinogens/pharmacologyCells, CulturedDeoxyguanine Nucleotides/immunology/*pharmacologyGuanosine 5'-O-(3-Thiotriphosphate)/pharmacologyGuanosine Diphosphate/metabolismHumansNADPH Oxidase/metabolismNeutrophils/*drug effects/metabolismRespiratory Burst/*drug effectsSuperoxides/*metabolismTetradecanoylphorbol Acetate/pharmacologyrac 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
DOI
https://doi.org/10.1080/10715760701250270
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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