• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Signal Transduction in Neutrophil Activation - Search for the real 2nd messenger

Research Project

Project/Area Number 05680613
Research Category

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

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionEhime University

Principal Investigator

TAMURA Minoru  Ehime University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (00128349)

Co-Investigator(Kenkyū-buntansha) OKUDA Hiromichi  Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (80035427)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
KeywordsNeutrophil / NADPH oxidase / Superoxide / Active oxygen / Signal transduction / Phosphatidic acid / Electroporation / Spermine
Research Abstract

We have searched for the signaling molecules which activate or inactivate the superoxide generating enzyme (NADPH oxidase) in neutrophils, and found that hosphatidic acid (PA) may activate the enzyme and spermine inactivate it.
PA is derived from phosphatidylcholine by action of phosphlipase D which is known to activate upon cell activation. When added to permeabilised neutrophils, PA elicited the activity immediately. The activation was found independent of Ca^<2+>, diacylglycerol, or protein kinase c. The activation was caused by PA micromolar concentrations. And the rate of O_2^- generation was similar to that by physiological stimuli. These results show that PA may searve as a second messenger to activate NADPH oxidase in the cell.
Spermine, a celular plyamine, down-regulates superoxide generation [Ogata, Tamura, Takeshita (1992) Biochem.Biophys.Res.Commun.] . In the present study, to elucidate the mechanism for the inhibition, the effect of spermine on cell-free activation of NADPH oxidase was examined. Spermine suppressed the SDS-induced activation of the oxidase (IC_<50>=18muM). The inhibition was specific for spermine over its precursor amines. Spermine did not alter the K_m for NADPH or the optimal concentration of SDS for the activation. The amine was found to inhibit semi-recombinant cell-free system and may interfere with the assembly of the enzyme components to form active complex especially by binding to p67phox, a cytosolic subunit.
These results show that superoxide generation is suppressed by spermine in resting neutrophils and clicited by phosphatidic acid which increases upon the cell stimulation.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Minoru Tamura: "Phosphatidic Acid-induced Superoxide Generation in Electropermeabilized Human Neutrophils" Arch.Biochem.Biophys.305. 477-482 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 田村実: "ホスファチジン酸によるヒト好中球スーパーオキシド産生の誘起-電気穿孔法を用いて-" 生化学. 65. 944 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 田村実: "スペルミンによる好中球NADPHオキシダーゼ無細胞活性化の抑制-セミリコンビナント系を用いた作用機序の検討" 生化学. 67. 936 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kenichi Ogata: "Spermine suppresses the activation of human neutrophil NADPH-oxidase in cell-free and semi-recombinant systems" Biochem.J.313. 549-554 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ogata, K., Nishimoto, N., Uhlinger, D.J., Igarashi, T., Takeshita, M., and Tamura, M.: "Spermine suppresses the activation of human neutrophil NADPH-oxidase in cell-free and semi-recombinant systems" Biochem.J.313. 549-554 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamura, M., Ogata, K., and Takeshita, M.: "Phosphatidic acid-induced superoxide generation in electro-permeabilized human neutrophils" Arch.Biochem.Biophys.305. 477-482 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamura, M., Ogata, K., and Takeshita, M.: "Induction of human neutrophil superoxide generation by phos-patidic acid using electroporation" Seikagaku. 65. 944 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamura, M., Ogata, K.Takeshita, M., Nisimoto, N.: "Inhibitory effect of spermine on cell-free activation of human neutrophil NADPH oxidase" Seikagaku. 66. 652 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tamura, M., Nishimoto, N., Uhlinger, D.J., Saeki, J.: "Suppression of the cell-free activation of neutrophil NADPH oxidas e byspermine-Study on the mechanism using semi-recombinant system" Seikagaku. 67. 936 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 田村 実: "スペルミンによる好中球NADPHオキシダーゼ無細胞活性化の抑制-セミリコンビナント系を用いた作用機序の検討" 生化学. 67. 936 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ogata Kenichi: "Spermine suppresses the activation of human neutrophil NADPH-oxidase in cell-free and semi-recombinant systems" Biochem.J.313. 549-554 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 田村実: "ヒト好中球NADPHオキシダーゼの無細胞活性化に及ぼすスペルミンの影響" 生化学. 66巻. 652- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Minoru Tamura: "Phosphatidic Acid-induced Superoxide Generation in Electro-permeabilized Human Neutrophils" Arch.Biochem.Biophys.305. 477-482 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田村実: "ホスファチジン酸によるヒト好中球スーパーオキサイド産生の誘起" 生化学. 65巻. 944- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田村実: "ホスファチジン酸によるヒト好中球スーパーオキシド産生の誘起-電気穿孔法を用いて-" 生化学. 65巻. 944 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minoru Tamura: "Phosphatidic Acid-induced Superoxide Generation in Electropermeabilized Human Neutrophils" Arch.Biochem.Biophys.305. 477-482 (1993)

    • Related Report
      1993 Annual Research Report

URL: 

Published: 1993-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi