| Project/Area Number |
09671558
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HIROTA Kiichi Kyoto Univ. Graduate Sch.Medicine assistant professor, 医学研究科, 助手 (00283606)
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| Co-Investigator(Kenkyū-buntansha) |
YODOI Junji Kyoto Univ.inst for Virus Research professor, ウイルス研究所, 教授 (80108993)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | cytokinemin / redox regulation / thioredoxin / glutaredoxin / transcription factor / Ap-1 / NAPK |
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| Research Abstract |
Oxidative stresses such as ultraviolet (UV) irradiation to mammalian cells triggers variety of oxystress responses including activation of transcription factors. Recently, activation of nuclear factor-kappa B (NF-kappaB) has been shown to be under oxido-reduction (redox) regulation controlled by thioredoxin (TRX), which is one of major endogenous redox-regulating molecules with thiol reducing activity. In order to elucidate where in the cellular compartment TRX participates in NF-kappaB regulation, we investigated the intracellular localization of TRX UVB irradiation induced translocation of TRX from the cytoplasm into the nucleus. In in vitro diamide-induced crosslinking study, we showed that TRX can associate directly with NF-kappaB p50. Overexpression of wild-type TRX suppressed induction of luciferase activity under NF-kappaB-binding sites in response to UV irradiation compared to the mock transfectant. In contrast, overexpression of nuclear-targeted TRX enhanced the luciferase activity. Thus, TRX seems to play dual and opposing roles in the regulation of NF-kappaB, In the cytoplasm, it interferes with the signals to IkappaB kinases and block the degradation of IkappaB.In the nucleus, however, TRX enhances NF-kappaB transcriptional activities by enhancing its ability to bind DNA.This two step TRX-dependent regulation of NP-kappaB complex, may be a novel activation mechanism of redox-sensitive transcription factors.
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