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Studies on the production active oxygens by neutrophils and its regulation.

Research Project

Project/Area Number 02670112
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

TAKESIGE Koichiro  KYUSHU UNIVERSITY FAC.OF MED. Associate Professor, 医学部, 助教授 (10037450)

Co-Investigator(Kenkyū-buntansha) SUMIMOTO Hideki  KYUSHU UNIVERSITY FAC.OF MED. Assistant Professor, 医学部, 助手 (30179303)
南里 宏樹  九州大学, 医学部, 助手 (80150415)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
KeywordsNeurophils / NADPHoxidase / Active oxygens / Superoxide / Signal transduction / GTP結合タンパク質 / ス-パ-オキサイド / チトクロムb_<558> / 細胞膜 / リン脂質
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.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Kunihiko Aoyagi: "Role of Mg^<2+> in activation of NADPH oxidase of human neutrophils:Evidence that Mg^<2+> acts through G-Protein" Biochem.Biophys.Res.Commun.186. 391-397 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hideki Sumimoto: "Cytochrome 6_<558>,a component of the phagocyte NADPH oxidase,is a tlauoprotein" Biochem.Biophys.Res,Commun.186. 1368-1375 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hideki Sumimoto: "Formation of a novel 20-hydroxylated metabolite of lipoxin A4 by human neutrophi microsomes" FEBS Lett.315. 205-210 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takanori Kitazono: "Activation of cultured bovine aortic endothelial cells by extracellular pyrimidine triphosphate" Int.J.Biochem.24. 1323-1327 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoichi Eto: "Succinate-dependent Lipid peroxidation and its prevention by reduced ubiguinone in beef heart submitochondrial particles" Arch.Biochem.Biophys.295. 101-106 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takashi Mitsyama: "Cyclic AMP inhibits the respiratory burst of electropermeabilized human neutrophils at a downstream of protein rcnase C" Biochim.Biophys.Acta. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyoshi Ishida: "Recent Advances in Cellular and Molecular Biology" Wegmann,R.J., 8 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koichiro Takeshige: "Proceedings of the 5th International Congress on Oxygen R〓〓icals" Yagi Kunio, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nozaki,M.,Takeshige,K.,Sumimoto,H.,& Minakami,S.: "Reconstitution of the partially purified membrane component of the superoxide-generating NADPH oxidase of pig neutrophils with phospholipid." J.Biochem.187. 335-340 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishida,K.,Takeshige,K.,& Minakami,S.: "Endothelin-l enhances superoxide generation of human neutrophils stimulated by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine." Biochem.Biophys.Res.Commun.173. 496-500 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishida,K.,Takeshige,K.,Yu,L.,Nunoi,H.,& Minakami,S.: "GTP-Dependent activation of neutrophil superoxide-producing NADPH oxidase in a cell-free system." Recent advances in cellular and molecular biology.4. 381-388 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Aoyagi,K.,Takeshige,K.,& Minakami,S.: "Effects of iodothyronines on chemotactic peptide-receptor binding and superoxide production of human neutrophils." Biochim.Biophys.Acta.1093. 223-228 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kwak,J.Y.,Takeshige,K.,Cheung,B.S.& Minakami,S.: "Bilirubin inhibits the activation of superoxide-producing NADPH oxidase in a neutrophil cell-free system." Biochim.Biophys.Acta.1076. 369-373 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [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
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Aoyagi,K.,Takeshige,K.,Sumimoto,H.,Nunoi,H.,& Minakami,S.: "Role of Mg^<2+> in activation of NADPH oxidase of human neutrophils:Evidence that Mg^<2+> acts throuth G-protein." Biochem.Biophys.Res.Commun.186. 391-397 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kitazono,T.,Takeshige,K.,& Minakami,S.: "Activation of cultured bovine aortic endothelial cells by extracellular pyrimidine triphosphate." J.Biochem.24. 1323-1327 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kunihiko Aoyagi: "Role of Mg^<2+> in activation of NADPH Oxidase of human neutrophils:Evidence that Mg^<2+> acts through G-Protein" Biochem.Biophys.Res.Commun.186. 391-397 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hideki Sumimoto: "Cytochrome b558,a component of the phagocyte NADPH Oxidase,is a flavoprotein" Biochem.Biophys.Res.Commun.186. 1368-1375 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hideki Sumimoto: "Formation of a novel 20-hydroxylated metobolite of lipoxis A4 by human neutrophi microsomes" FEBS Lett.315. 205-210 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takanari Kitazono: "Activation of Cultured bovine aortic endothelial cells by extracellular pyrimidine triphosphate" Int.J.Biochem.24. 1323-1327 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoichi Eto: "Succinate-dependent Lipid peroxidation and its prevention by reduced ubiguinone in beef heart submitochondrial particles" Arch.Biochem.Biophys.295. 101-106 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takashi Mitsyama: "Cyclic AMP inhibits the respiratory burst of electropermeabilized human neutrophils at a dounstream of protein Rinase C" Biochim.Biophys.Acta. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kiyoshi Ishida: "Recent Advances in Cellular and Molecular Biology" Wegmann,R.J., 8 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Koichiro Takeshige: "Proceedings of the 5th International Congress on OXygen Radicals" Yagi Kunio, (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kwak,Jong Y.: "Bilirubin inhibits the activation of superoxideーproducing NADPH oxidase in a neutrophil cellーfree system" Biochim.Biophys.Acta. 1076. 369-373 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Aoyagi,Kunihiko: "Effects of iodothyronines on chemotactic peptideーreceptor binding and superoxide production of human neutrophils" Biochim.Biophys.Acta. 1093. 223-228 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kang,Dongchon: "Evidence that the decarboxylation reaction occurs before the first methylation in ubiquinone biosynthesis in rat liver mitochondria" Eur.J.Biochem.198. 599-605 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kang,Donchon: "Ubiquinone biosynthesis by mitochondria,sonicated mitochondria and mitoplasts of rat liver" J.Biochem.111. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 竹重 公一朗: "好中球の生理と病理" 代謝. 29. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takeshige,Koichiro: "Proceedings of the 5th International Congress on Oxygen Redicals" Yagi,Kunio, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ishida,Kiyoshi: "Proceedings of the 1st World Congress of Cellular Molecular Biology" Wegmann,R.J., (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nozaki,M.: "Reconstitution of the partially purified membrane component of the superoxideーgenerating NADPH oxidase of pig neutrophils with phospholipid" Eur.J.Biochem.187. 335-340 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hasegawa,E.: "1ーMethylー4ーPhenylpyridinum(MPP^+) induces NADHーdependent superoxide formation and enhances NADHーdependent lipidperーoxidation in bovine heart submitochondrial particles" Biochem.Biophys.Res.Commun.170. 1049-1055 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kang,D.: "An intermediate of ubiquinone biosynthesis exists in the microsomal fraction of HepG2 cells" J.Biochem.108. 893-895 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ishida,K.: "Endothelinー1 enhances superoxide generation of human neutrophils stimulated by the chemotactic peptide Nーformylーmethionylーleucylーphenylalanine" Biochem.Biophys.Res.Commun.173. 496-500 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kwak,Y.: "Bilirubin inhibits the activation of superoxideーproducing NADPH oxidase in a neutrophil cellーfree system" Biochim.Biophys.Acta. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 水上 茂樹・柿沼 カツ子・竹重 公一朗/編: "白血球と生体防御" 講談社サイエンティフィク, 272 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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