| Project/Area Number |
14572073
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
HAYAKAWA Makio Tokyo Univ.Pharm.& Life Sci., Dept.Pharm., Associate Professor, 薬学部, 助教授 (30198824)
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| 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)
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| Keywords | NF-kB / IkB / reactive oxygen species / antioxidant / Rac / NADPH oxidase / NAC / PDTC / 活性酵素 / Pac |
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| 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.
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