| Project/Area Number |
01440084
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
IMURA Nobumasa Kitasato University School of Pharmaceutical Sciences,Professor, 薬学部, 教授 (70012606)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshiko Kitasato University School of Pharmaceutical Sciences,Research Associate, 薬学部, 助手 (40188313)
HIMENO Seiichiro Kitasato University School of Pharmaceutical Sciences,Research Associate, 薬学部, 助手 (20181117)
TOYODA Haruka Kitasato University School of Pharmaceutical Sciences,Research Associate, 薬学部, 助手 (10197973)
SEKO Yoshiyuki Kitasato University School of Pharmaceutical Sciences,Lecturer, 薬学部, 講師 (60133360)
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| Project Period (FY) |
1989 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥29,400,000 (Direct Cost: ¥29,400,000)
Fiscal Year 1992: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1991: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1990: ¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1989: ¥14,000,000 (Direct Cost: ¥14,000,000)
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| Keywords | Metallothionein / Superoxide dismutase / Glutathione peroxidase / Catalase / Active oxygens / Free radicals / Transormation / Antisense RNA / ス-パ-オキシドジスムタ-ゼ / グルタチオンペルオキシダ-ゼ / カタラ-ゼ / フリ-ラジカル除去因子 / antisense RNA |
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| Research Abstract |
Lethality of paraquat (PQ) in mice was remarkably reduced by pretreatment with each one of MT-inducing metals (Zn,Cu,Bi,Co,Cu,or Hg). The protective effect by pretreatment with these metals on PQ lethality was significantly correlated with MT levels in the lung,a target tissue of PQ toxicity. The increase in pulmonary lipid peroxidation in mice treated with PQ was remarkably depressed by Zn pretreatment. Zn was the most effective in protecting against PQ lethality among the above MT-inducing metals used in this study. Futhermore,similar protecting effects by Zn pretreatment against the lethality of carbon tetrachloride and menadione were obseved in mice.
Transformant cell lines overproducing mouse MT-I,superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) and catalase (CL), designated TF-MT,TF-SOD,TF-GPx and TF-CL,respectively,were established by introducing the corresponding cDNAs into human HeLa S3 cells. TF-MT lines were more resistant to Cd than the parental HeLa cells and showed good correlation between the degree of Cd resistance and the cellular MT level. TF-GPx,TF-CL and TF-SODshowed significant resistance to H_2O_2 and PQ,respectively,than their parent cells. The extent of resistance to these toxic reagents were well correlated with the elevated level of GSH-Px,CL or SOD activity in each transformant. In addition,TF- GPx were less sensitive to organic peroxides such as cumene hydroperoxide and t-butyl hydroperoxide than the parent strain. TF-CL was revealed to be useful cell line to detect H_2O_2 generation within cessl caused by oxidative stress inducing chemicals by using aminotriazole (AT),an H_2O_2-dependent CL inhibitor. Because the strain has sufficiently high CL activity both in cytosol and peroxisome fractions even after AT pretreatment to detect additional H_2O_2 formation by the chemicals added in the medium.
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