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Re-evaluation of the role of reactive oxygen species in NP-kB signaling

Research Project

Project/Area Number 14572073
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

HAYAKAWA Makio  Tokyo Univ.Pharm.& Life Sci., Dept.Pharm., Associate Professor, 薬学部, 助教授 (30198824)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsNF-kB / IkB / reactive oxygen species / antioxidant / Rac / NADPH oxidase / NAC / PDTC / 活性酵素 / Pac
Research Abstract

It has been postulated that reactive oxygen species(ROS)may act as the second messengers leading to NP-kB activation.This hypothesis is mainly based on the findings that N-acetyl-L-cysteine(NAC) and pyrrolidine dithiocarbamate (PDTC), compounds recognized as potential antioxidants, can inhibit NF-kB activation in a wide variety of cell types.Here we reveal that both NAC and PDTC inhibit NF-KB activation independently of antioxidative function. NAG selectively blocks TNF-induced signaling by lowering the affinity of receptor to TNF.PDTC inhibits the IkB-ubiquitin ligase activity in the cell-free system where extracellular-stimuli-regulated ROS production does not occur.Furthermore, we present the evidence that endogenous ROS produced through Rac/NADPH oxidase do not mediate NF-kB signaling but instead they lower the magnitude of its activation.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Makio Hayakawa: "Evidence that reactive oxygen species do not mediate NF-κB activation"EMBO J.. 22. 3356-3366 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayakawa, M., Miyashita, H., Sakamoto, I., Kitagawa, M., Tanaka, H., Yasuda, H., Karin, M., Kikugawa, K.: "Evidence that reactive oxygen species do not mediate NF-kB activation"EMBO J.. 22. 3356-3366 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Makio Hayakawa: "Evidence that reactive oxygen species do not mediate NF-κB activation"EMBO J.. 22. 3356-3366 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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