| Project/Area Number |
10557217
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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 |
Biological pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAGANUMA Akira Graduate School of Pharmaceutical Sciences, Tohoku University, Professor, 大学院・薬学研究科, 教授 (80155952)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Shoji Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., Manager, 薬品総合研究所, 主席研究員
MIURA Nobuhiko Graduate School of Pharmaceutical Sciences, Tohoku University, Research Associate, 大学院・薬学研究科, 助手 (20229644)
MIYAIRI Shinichi Graduate School of Pharmaceutical Sciences, Tohoku University, Associate Professor, 大学院・薬学研究科, 助教授 (50209855)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1998: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Metallothionein / Kidney / Cadmium / Polymorphism / Promoter / Renal injury / 遺伝子発現 / 脳 |
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| Research Abstract |
Nuclear localization metallothionein (MT) in mammalian cells has been reported, indicating that metallothionein may also be associated with unclear functions. We speculated that MT is involved in gene expression. Genes differentially expressed in association with disruption of the MT gene were screened using two hepatic cell lines isolated and established from the livers of normal and transgenic mice deficient in the genes for MT-1 and -2 (MT-null). We found one cDNA (NM31) that was expressed only in normal cells. The nucleotide sequence of NM31 was identical to the 3' region of PTZ 17, which is related to pentylenetetrazol (PTZ)-induced seizures. Transfecting MT-null cells with the genes for both MT-1 and -2 resulted in NM31 expression. High expression level of NM31 has been observed in the brain of human and mouse. The expression of NM31 was also observed in the brain of MT-null mouse which is containing brain specific Mt isoform, MT-3. When the MT-3 gene was introduced into the MT-null cells, the expression of the NM31 gene was also observed, suggesting an important role of MT-3 in expression of NM31 in the brain. On the other hand, MT is known that the synthesis was induced by heavy metals such as zinc. However, the NM31mRNA level in normal cells was not changed by zinc at a concentration sufficient to induce MT. It seems that MT levels of the normal cell are enough for the expression of NM31. Significant difference of cytotoxicity of PTZ could not be recognized between MTnull-cell and normal. Next, we examined cytotoxicity of PTZ in MT-null cells and normal cells. Significant difference of cytotoxicity of PTZ could not be recognized between these two cell lines, suggesting that NM31 may not be involved in PTZ toxicity.
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