| Project/Area Number |
13670137
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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 |
Pathological medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MASUTANI Hiroshi INST. FOR VIRUS RES., KYOTO UNIV., ASSISTANT PROFESSOR, ウイルス研究所, 助手 (50252523)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masayuki TARA CENTER, TSUKUBA UNIV., PROFESSOR, 先端領域学際センター, 教授 (50166823)
YODOI Junji INST. FOR VIRUS RES., KYOTO UNIV., PROFESSOR, ウイルス研究所, 教授 (80108993)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Oxidative stress / thioredoxin / promoter / ARE / Nrf2 / signal transduction / NGF / CRE / NFG / 神経突起伸長 / シグナル伝達 / アポトーシス / ダイオキシン / 転写因子 / ヘミン |
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| Research Abstract |
AIM: We investigated the function of thioredoxin (TRX) by analyzing activation mechanism of the thioredoxin gene.
RESULTS: 1) We demonstrated that the TRX gene is induced by hemin or tertial butylhydroquinone (tBHQ) through antioxidant responsive element (ARE) by Nrf2. We showed a mechanism of a differential regulation of the antioxidant responsive element (ARE) by a switch of its binding factors. We also showed TRX -dependent redox regulation of the ARE in electrophile response (JBC, 2001; Oncogene, 2003). These results suggest the role of TRX in erythroid differentiation and host defense against reperfusion injury and chemical carcinogensis.
2) We demonstrated that the TRX gene is induced by nerve growth factor (NGF) through cyclic AMP responsive element by CREB. We also showed critical Roles of TRX in NGF-Mediated Signal Transduction and Neurite Outgrowth in PC 12 Cells. (J. of Neuroscience, 2003).
3) We cloned mouse TRX genome and are preparing t TRX knock-down mice. We also prepared TRX RNAi vector. We analyzed TRX binding protein-2 (TBP-2), a negative regulator of t TRX and are preparing TBP-2 knock out mice and transgenic mice.
4) We showed a mechanism of oxidative stress-induced apoptosis (EMBO J., 2002). We showed a mechanism of apoptosis by 3-methylcholanthrene, a polycyclic aromatic hydrocarbon (JBC, 2002).
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