Project/Area Number |
03454159
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Pathological medical chemistry
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
UEDA Kunihiro Kyoto Univ. Fac. of Med Dept. of Lab. Med. Assoc. Prof., 医学部, 助教授 (00027070)
|
Project Period (FY) |
1991 – 1992
|
Project Status |
Completed (Fiscal Year 1992)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | Poly(ADP-ribose) / Enzyme inhibitor / ADP-ribosyltransferase / Enzyme activator / Cell differentiation / Teratocarcinoma / Vesnarinone / Bloom syndrome / ポリ(ADPーリボース) / ADPーリボシルトランスフェラーゼ / ポリ(ADPーリボシル)化 / ポリ(ADPーリボ-ス)シンテタ-ゼ / 阻害剤 / 細胞分化の誘導 / テラトカルシノ-マ細胞 / モノ(ADPーリボシル)トランスフェラ-ゼ / ビタミンK / カルシウムイオン |
Research Abstract |
1. Inhibitors of ADP-ribosylation: From among >400 organic compounds, we found many strong inhibitors of poly(ADP-ribose) synthetase. Part of them proved to be inhibitory to mono(ADP-ribosyl)transferases. 2. Activators of poly(ADP-ribosyl)ation: We found activation of poly(ADP-ribose) synthetase by metal ions, organic solvents, polyanions, chelators, and carboline compounds. 3. Tumor cell differentiation: We found the action of 4-hydroxyquinazoline and other new inhibitors to induce endothelial differentiation of teratocarcinoma EC cells in culture. 4. Vesnarinone: We found vesnarinone and its derivatives to inhibit poly(ADP-ribose) synthetase and induce EC cell differentiation into neuronal or glial cells. 5. Calcium ion: We found correlation between poly(ADP-ribose) synthetase activity and Ca^<++> concentrations in differentiation-induced epidermal transformed cells. 6. Bloom syndrome: We found an abnormally low activity of poly(ADP-ribose) synthetase in lymphocytes of low-SCE type Bloom syndrome.
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