| Project/Area Number |
09670155
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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 | Tottori University |
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Principal Investigator |
SATO Kenzo Tottori University Faculty of Medicine, Professor, 医学部, 教授 (40113196)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Naohiro Tottori University Faculty of Medicine, Research Associate, 医学部, 助手 (80263466)
ITO Keizo Tottori University Faculty of Medicine, Instructor (40213037)
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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 |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Reactive oxygen / Gene expression / Catalase / Redox control / Transcription factor / Liver specific genes / Liver function / プロモーター |
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| Research Abstract |
Reactive oxygen induces various diseases via an irregular control of gene expressions. In this study, we isolated and characterized redox-controlled transcription factor (Box A protein) bound to the rat catalase gene promoter, in- order to disclose the mechanism for aberrant regulation of catalase gene transcription under the condition of shifted redox state. Moreover, we identified hepatocyte nuclear factor (HNF-3G) as a key factor for catalase gene expression.
The rat catalase gene promoter bearded inverted-repeated elements on both sides of transcription initiation site. The Box A protein bound to the elements, and was rearranged the binding activity by redox regulator such as hydroxyl peroxide. This factor composed as. four proteins complex, and the molecular weight of these components were estimated as -50, 38,30. and 20 kDa. Furthermore, hydroxyl peroxide-induced neuronal cell death was analyzed with genetic sopngiform encepharopathy rat brain, and was shown to be involved in upregulation of Ref- 1 protein responded to redox state.
On the other hand, HNF-3G, which is a hepatocyte enriched transcription factor and a determinant for differentiation of liver cells, was involved in regulation of catalase gene expression. Recombinant adenovirus carrying this gene showed hepatoconservation effect in the infected primary hepatocyte that lost the most of liver function. Moreover, pretreatment of the rat liver with this vector revealed hepatoprotection effect for hepato-injury regent like a tetrachlorocarbon (CCl4) generating superoxide.
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