1993 Fiscal Year Final Research Report Summary
Mechanism of Action of Lactacystin, a Microbial Substance Having NGF-like Action
| Project/Area Number |
04671367
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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 |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
TANAKA Haruo Kitasato University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40118823)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Masako Kitasato University, School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (60255362)
MATSUZAKI Keiichi Kitasato University, Schol of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (20229454)
IKEDA Hodaka Kitasato University, School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (70232197)
IKEDA Haruo Kiasato University, School of Pharmaceutical Sciences, Associated Professor, 薬学部, 助教授 (90159632)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Lactacystin / Trichostatin A / C alyculin A / Mechanism of action / Cell cycle / Neuro 2a cells / Neurite / NGF-like action |
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| Research Abstract |
The following results were obtained in the study of the mechanism of action of the microbial neuritogenesis inducer lactacystin in Neuro 2a cells.
1. Acetylcholineesterase activity in the cells was significantly enhanced by the treatment with lactacystin (1.3muM). Thus, lactacystin was proved functionally in addition to morpholotgically to induce the differentiation of Neuro 2a cells.
2. The mechanism of action of actacystin was proved to be differentiated from those of cAMP level enhancing substances (dibutyry1-cAMP, forskolin etc.) and protein kinase inhibitors (H-7 etc.) which are known to induce neuritogenesis in the cells.
3. Calycuin A, a protein phosphatase inhibitor, was shown to inhibit dipolar neurite outgrowth occurred in 1 day after the treatment with lactacystin, sugtgesting that protein hosphatases are involved in the dipolar neutite outgrowth. Hoever, calyculin A did not affect the formation of the network 3days after the treatment.
4. Lactacystin inhibits the cell cycle of Neuro2a cell by G1/G2 arrest. Furthermore, the histone deacetylase inhibitors trichostatin A (270nM) was found to induce neuritegenesis in the cells. The network induced with tricostatin A was kept for at least 21days.
5. Total synthesis of lctacystin was established with a high yield.
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