| Project/Area Number |
12557015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
YAMAMOTO Masayuki University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (50166823)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Makoto University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (50254941)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | electrophiles / xenobiotics / transcriptional regulation / chemicals / Nrf2 / oxidative stress / mouse / zebrafish / 環境異物 / モデル動物 / bZip型転写因子 / bHLH-PAS型転写因子 |
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| Research Abstract |
Analysis using Nrf2-LacZ mice
After feeding NrfZ-LacZ mice with dietary BHA for 3 days, accumulation of LacZ activity was observed in intestine, liver and peritoneal macrophages. The result suggested that Nrf2-LacZ mice are useful for detecting toxic chemicals in foods or medicines. In addition, we found a posttranseriptional accumulation of Nrf2 protein in response to electrophiles.
Analysis of Nrf2 knockout mice
Nrf2 knockout mice was susceptible to benzo[o]pyrene-induced neoplasia in the forestomach, diesel exhaust-induced hyperplasia and oxidative DNA adduct formation in the lung, and acetaminophen-induced hepatotoxicity. These results demonstrated that Nrf2 knockout mice are highly sensitive to carcinogen and/or oxidative stress, and that they will be useful for detecting toxic chemicals in foods or medicines.
Zebrafish system for xenobiotic studies
We showed that Nrf2-based induction of phase II detoxifying enzymes was conserved in fish and that a possibility of monitoring carcinogens using zebra fish system. Thus the GFP reporter construct fused to the transcriptional regulatory region of zebrafish GSTpi gene was prepared. In a transient reporter analysis, we could observed a GFP induction by electrophiles in zebra fish larvae. We are now trying to establish a stable transgenic zebrafish line which contains the construct.
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