1993 Fiscal Year Final Research Report Summary
Development of methodology for investigation of polyamine-macromolecule interaction in living cells
| Project/Area Number |
03671029
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | JOSAI UNIVERSITY |
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Principal Investigator |
SAMEJIMA Keijiro Josai Univ., Fac. of Pharm. Sci., Professor, 薬学部, 教授 (00072413)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAHATA Akira Josai Univ., Fac. of Pharm. Sci., Docent, 薬学部, 講師 (50150107)
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| Project Period (FY) |
1991 – 1993
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| Keywords | 5-Carboxyspermine / HTC cells / Polyamine analogues / Hypusine / Apoptosis / Spermidine synthase / spermidine / DEcarboxylated S-adnosylmethionine |
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| Research Abstract |
1) Evaluation of 5-carboxystermine (5-CS) as a tool for functional studies of polyamine : Derivatives of 5-CS, having various functional melecules at the carboxyl group with amede bond linkage, were tested for shether or not their spermine backbone behaves simikar to spermine, using an assay system of inhibition of DNA-ethidiumbromide complex formation. The results showed that their property was similar to that of spermidine due to lowerd basicity of the secondary amine at the alpha position of 5-chrboxamide group. A compund such as 6-carboxyspermine instead of 5-CS will be thus fit for the purpose. 2) Regulation of polyamine metabolism in HTC cells : (1) New inhibitors of aminopropyltransferases- A potent inhibitor for spermidine syntase, trans-4-methylcyclohexylamine, lowered intracllular spermidine concentration to less than 2 % that of control cells, and showed no effect on both spermine concentration and cell growth. And a potent inhibitor for spermine synthase, N-(3-aminopropyl)cyclohexylamine, lowered intracellular sprmine concentration to less than 1 % that of cantrol cells, and showed no effect on cell growth with a high level of spermidine concentration. (2) Application of spermidine analogues to polyamine depleted cells - When various spermidine analogues were added to temporarily repressed cells in growth, treated with an ODC inhibitor, 1-aminoxy-3-aminopropane (AOAP), the cells usually grew for a few days, and then stopped growing. These phenomena were explained, after a series of experiments, by an sessentiality of spermidine for cell growth. (3) An explanation for essentiality of spermidine - The role of spermidine in hypusine synthesis was considered, and hypusine was determined. A good relation ship was ocbserved between the process of cell growth to cessation after addition of spermidine analogues and decreasing concentration of hypusine. (4) Cell death in accordance with an accumulation of excess spermidine - When spermidne was added to the AOAP-
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Research Products
(9 results)
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[Publications] Frydman,L.,Rossomando,P.C.,Frydman,V.,Fernandez,C.O.,Frydman,B.,Samejima,K.: "Interaction between natural polyamines and tRNA:An ^<15>N NMR analysis" Proc.Natl.Acad.Sci.USA. 89. 9186-9190 (1992)
Description
「研究成果報告書概要(和文)」より
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[Publications] Basu,H.S.,Pellarin,M.,Feuerstein,B.G.,Shirahata,A.,Samejima,K.,Deen,D.F.and Marton,L.J.: "Interaction of a polyamine analogue,1,19-bis-(Ethylamino)-5,10,15-triazanonadecane(BE-4-4-4-4),with DNA and effect on growth,survival,and polyamine levels in seven human brain tumor cell lines" Cancer Research. 53. 3948-3955 (1993)
Description
「研究成果報告書概要(和文)」より
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[Publications] Frydman, L., Rossomando, P.C., Frydman, B., Fernandez, C.O., Frydman, b. and Samajima, K.: "Interaction between natural polyamines and tRNA : An ^<15>N NMR analysis." Proc. Natl. Acad. Sci. USA. 89. 9186-9190 (1992)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Basu, H.S., Pellarin, M., Feuerstein, B.G., Shirahata, A., Samejima, K., Deen, D.F.and Marton, L.J.: "Iteraction of a polyamine Analogue, 1, 19-bis-(Ethylamino)-5, 10, 15-triazanonadecane (BE-4-4-4-4), with DNA and Effect on Growth, Survival, and Polyamine Levels in Seven Human Brain Tumor Cell Lines." Cancer Research. 53. 3948-3955 (1993)
Description
「研究成果報告書概要(欧文)」より
