Polyamines in 1 ,25-Dihydroxycholecalciferol-Induced Differentiation of Human Promyelocytic Leukemia Cells, HL-60
| Project/Area Number |
60480275
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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 |
内分泌・代謝学
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| Research Institution | Osaka City University |
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Principal Investigator |
MORII Hirotoshi 2nd Dept of Internal Medicine, Osaka City Univ. Medical School, 医学部, 教授 (40046983)
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| Co-Investigator(Kenkyū-buntansha) |
OTANI Shuzo Dept of Biochemistry, Osaka City Univ. Medical School, 医学部, 助教授 (80047068)
INABA Masaaki 2nd Dept of Internal Medicine, Osaka City Univ. Medical School, 医学部, 助手 (00176405)
NISHIZAWA Yoshiki 2nd Dept of Internal Medicine, Osaka City Univ. Medical School, 医学部, 講師 (00128745)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | vitamin D / HL-60 cells / Differentiation / Polyamine / Ornithine Decarboxylase / Spermidine / スペルジン-´N-アセチルトランスフェラーゼ |
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| Research Abstract |
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/ monocyte in the presence of 1 <alpha> ,25-dihydroxycholecalciferol (1 <alpha> ,25 <(OH)_2> <D_3> ), as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase (ODC) and spermidine/spermine- <N^1> -acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 <alpha> ,25 <(OH)_2> <D_3> and then decreaesd, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of <alpha> -difluoromethylornithine, inhibtor of ODC, with or without methylglyoxalbis (guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase,caused no effect on 1 <alpha> ,25 <(OH)_2> <D_3> -induced cell differentiation, although the cellular level of putrescine and spermidine decreased markedly. Addition of <alpha> -difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 <alpha> ,25 <(OH)_2> <D_3> -induced cell differentiation. These results suggest that polyamine metabolism is not important in 1 <alpha> ,25 <(OH)_2> <D_3> -induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.
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Report
(1 results)
Research Products
(2 results)
