| Project/Area Number |
10672070
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokuriku University |
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Principal Investigator |
OHYASHIKI Takao Hokuriku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00100488)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Eiko Hokuriku University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (20298368)
TAKADERA Tsuneo Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90121277)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | aluminum / aluminum toxicity / cell death / apoptosis / nerve growth factor (NGF) / aluminum-maltolate / PC12 cell / 神経成長因子 / 細胞障害 |
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| Research Abstract |
Cytotoxic effects of aluminum ions PC12 cells were examined using aluminum-maltolate complex (Almal) and AlClィイD23ィエD2.
1. Exposure PC12 cells to various concentrations (0.1〜1 mM) of AlClィイD23ィエD2 for 3 days caused cell morphological change and cell aggregation, but appreciable changes in LDH and MTT activities were not detected. In addition, chromatin condensation and DNA fragmentation were also not detected by treatment of PC12 cells with AlClィイD23ィエD2 even at high concentration (1 mM) of the salt.
2. On the other hand, treatment of the cells with Almal (300 μM) showed marked increases of trypan blue-stained cells and LDH release, decrease of MIT activity, chromatin condensation and DNA fragmentation, as well as morphological change and cell aggregation. In addition, there is a good correlation between the amount of Almal incorporated ang the extents of LDH release and MIT activity. From these results, it is concluded that Almal-mediated cell damage proceeds via apototic cell death, depending on the amount of Almal incorporated into the cells.
3. Nerve growth factor (NGF) effectively prevented Almal-mediated cell death, assessed by trypan blue-staining, LDH and MIT activities, H33258 staining (chromatin condensation) and DNA ladder. The concentration of NGF required to induce 50% inhibition of Almal-mediated cell death (ECィイD250ィエD2) was 25 ng/ml. Pretreatment of PC12 cells with anti-NGF completely disappeared the protection effect of NGF against Almal-mediated cell death. These results proposed the possibility that a signal transmission pathway via NGF receptor is partly involved in the development of Almal-mediated cell death.
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