| Project/Area Number |
03453141
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
製造化学・食品
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| Research Institution | University of Tokyo |
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Principal Investigator |
SETO Haruo Inst. Appl. Microbiol., Univ. of Tokyo, Professor, 応用微生物研究所, 教授 (10013335)
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| Co-Investigator(Kenkyū-buntansha) |
FURIHATA Keiko Inst. Appl. Microbiol., of Univ. Tokyo, Assistant, 応用微生物研究所, 教務職員
IKEDA Keiji Inst. Appl. Microbiol., Univ. of Tokyo, Assistant, 応用微生物研究所, 教務職員 (50092127)
HAYAKAWA Yoichi Inst. Appl. Microbiol., Univ. of Tokyo, Assoc. Prof., 応用微生物研究所, 助教授 (20208606)
島津 昭 東京大学, 応用微生物研究所, 助手 (50092234)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | cell growth promoter of low molecular weight / lavanducyanin / exfoliazone / resorcinin / misakimycin / ラバンドアニン / プロテインキナ-ゼの活性化 / カルシウム濃度の増大効果 |
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| Research Abstract |
None proteinous microbial metabolites with low molecular weight are expected to be useful for studying cell growth mechanisms as well as for reducing production cost of proteins such as growth factors and hormones produced by animal cells. Our screening for such compounds resulted in isolation of four unique metabolites; lavanducyanin from Streptomyces aeriouvifer, exfoliazone from Streptomyces exfoliatus, resorcinin from a gliding bacterium, Cytophaga johnsonae and misakimycin from Streptomyces misakiensis. All of these metabolites were lipophilic and purified by solvent extraction followed by appropriate chromatographies. Their structures were determined mainly based on NMR spectral analysis to be as follows; lavanducyanin, a phenazine derivative with an alkyl substituent; exfoliazone, a substituted phenoxazinone; resorcinin, 2-isoundecy1-5-isohexyl-resorcinol; misakimycin, 5-hydroxy-2,7-dimethoxy-6-methyl-1,4-naphthoquinone.
These derivatives showed strong growth promoting activities to some kind of animal cell lines at lower serum concentrations. However, no effect was observed under serum-free conditions. Their activities were analyzed by MTT assay and by the increases of cell number and DNA synthesis, and their effective doses were determined at the range of nanogram to microgram/ml.
Since the growth stimulating effect were observed with same kinds of cell lines including RLN-8, NIH 3T3 and T601, their action mechanisms seem to be identical. Since the famous tumor promoter TPA was inactive under the same condition, the action mechanisms of the compounds isolated by this work are concluded to be different from that of TPA.
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