8-oxo-7,8-dihydroguanosine triphosphate(8-oxoGTP) down-regulates respiratory burst of neutrophils by antagonizing GTP toward Rac, a small GTP binding protein. 2007

Hee Joon Kim, and Sun-Hee Yoon, and Hyun-Ok Ryu, and Byung-Hak Yoon, and Seongwon Choi, and Sang-Kyu Ye, and Myung-Hee Chung
Department of Pharmacology, Eulji University School of Medicine, Daejeon, South Korea.

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.

UI MeSH Term Description Entries
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003848 Deoxyguanine Nucleotides Guanine nucleotides which contain deoxyribose as the sugar moiety. Deoxyguanosine Phosphates,Nucleotides, Deoxyguanine,Phosphates, Deoxyguanosine
D006153 Guanosine Diphosphate A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. GDP,Guanosine 5'-Diphosphate,Guanosine 5'-Trihydrogen Diphosphate,5'-Diphosphate, Guanosine,5'-Trihydrogen Diphosphate, Guanosine,Diphosphate, Guanosine,Diphosphate, Guanosine 5'-Trihydrogen,Guanosine 5' Diphosphate,Guanosine 5' Trihydrogen Diphosphate
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D013481 Superoxides Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides. Superoxide Radical,Superoxide,Superoxide Anion
D013755 Tetradecanoylphorbol Acetate A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA. Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D016244 Guanosine 5'-O-(3-Thiotriphosphate) Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes. GTP gamma S,Guanosine 5'-(gamma-S)Triphosphate,gamma-Thio-GTP,GTPgammaS,Guanosine 5'-(3-O-Thio)Triphosphate,gamma S, GTP,gamma Thio GTP

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