1992 Fiscal Year Final Research Report Summary
Studies on the production active oxygens by neutrophils and its regulation.
| Project/Area Number |
02670112
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TAKESIGE Koichiro KYUSHU UNIVERSITY FAC.OF MED. Associate Professor, 医学部, 助教授 (10037450)
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| Co-Investigator(Kenkyū-buntansha) |
SUMIMOTO Hideki KYUSHU UNIVERSITY FAC.OF MED. Assistant Professor, 医学部, 助手 (30179303)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Neurophils / NADPHoxidase / Active oxygens / Superoxide / Signal transduction |
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| Research Abstract |
(1)Studies in a cell-free system
(i) We solubilized the membrane component of the NADPH oxidase and fractionated by chromatography on agarose-linked wheat germ agglutinin(WGA).Although each fraction showed no potency for the O_2^--generating activity in a cell-free activation system,that of the membrane component was reconstituted from the fraction passing through the column and that eluted with N-acetylglucosamine.The former fraction could be replaced by a phospholipid,such as azolectin.
(ii) We found that Mg^<2+> seems to modulate the activation of the NADPH oxidase at the level of the G-protein.
(iii) Because the alignments of the amino acid sequence of the large subunit of the cytochrome b_<558> with those of previously characterized flavoproteins revealed that the middle and C-terminal portions of the cytochrome are likely to be FAD-and NADPH-binding domains,respectively, cytochrome b_<558> appears to be a flavoprotein with an NADPH-binding site of the NADPH oxidase.
(iv) The effect of bilirubin on the NADPH-dependent O_<2"> production was studied in a cell-free system,and the results indicate that bilirubin inhibits the activation process of the NADPH oxidase by decreasing the potency of the cytosolic fraction.
(2) Studies with intact or electropermeabilized neutrophils
(i) We studied the action of iodinated thyronines of O_2^- production of human neutrophils stimulated by a chemotactic peptide,FMLP,in vitro and found that thyroxine and tri iodothyronine interfere with the binding of FMLP to the receptor,leading to the inhibition of neutrophil functions such as O_2^- production.
(ii) We showed by using electropermeabilized human neutrophils that c AMP inhibited the activation of the NADPH oxidase not only the at the site before the protein kinase C but also at another site after the kinase.
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[Publications] Sumimoto,H.,Sakamoto,N.,Nozaki,M.,Sakaki,Y.,Takeshige,K.,& Minakami S.: "Cytochrome b_<558>,a component of the phagocyte NADPH oxidase,is flavoprotein" Biochem.Biophys.Res.Commun.186. 1368-1375 (1992)
Description
「研究成果報告書概要(欧文)」より
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