CELL DEATH AND POLYAMINE

细胞死亡和多胺

基本信息

批准号：
06807173
负责人：
SHIRAHATA Akira
金额：
$ 1.15万
依托单位：
JOSAI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807173/
关键词：
Polyamine Spermidine Cell death Polyamine oxidase Polyamine transport Diacetylpolyamine アポトーシス

项目摘要

It was found that administration of spermidine to cultured rat hepatoma (HTC) cells depleted of polyamine with ornithine decarboxylase inhibitor, 1-aminooxy-3-aminopropane (AOAP), 1ed to an abnormal accumulation of cellular spermidine followed by the cell death. although, some morphorogical features suggested it was apoptosis, mitocondrial damage was observed in electron micrograph and a clear fragmentation of DNA was not observed in the analysis of cellular DNA by gel electrophoresis.Mechanism of tha abnormal accumulation of spermidine was examined. It was found that the accumulation was dependent on the exposure period of AOAP to the cells, and that the longer exposure of AOAP inhibited repression of spermidine uptake activity. As protein synthesis rate was decreased to 20% of control by the longer exposue of AOAP,it was suggested that inhibition of synthesis of a protein by the long exposure of AOAP to the cells which was needed in the repression of spermidine uptake activity led to the abnormal accumulation of spermidine.In order to develope a prodrug which enable us to introduce excess polyamine into cells diacetly derivatives of polyamine were synthesized and examined. It was found that diacetyl pentaamines were good substrates of polyamine uptake system and polyamine oxidase, and then efficiently converted into spermidine or norspermidine in HTC cells. But these compounds were not successfully taken into the cells to an abnormal accumulation level, suggesting that the srtucture which does not utilize polyamine transport system is needed for the compound to be accumulate to excess level in cells.

结果发现，用鸟氨酸脱羧酶抑制剂，1-氨基氨基3-氨基丙烷（AOAP）对多胺耗尽的培养大鼠肝癌（HTC）细胞的给药，1ED至异常的细胞杀虫剂，随后细胞死亡。尽管某些形态学特征表明它是凋亡，但在电子显微照片中观察到了线粒体损伤，并且在通过凝胶电泳的分析中观察到DNA的明显碎片。发现积累取决于AOAP对细胞的暴露周期，并且更长的AOAP暴露抑制了精子摄取活性的抑制。 As protein synthesis rate was decreased to 20% of control by the longer exposue of AOAP,it was suggested that inhibition of synthesis of a protein by the long exposure of AOAP to the cells which was needed in the repression of spermidine uptake activity led to the abnormal accumulation of spermidine.In order to develope a prodrug which enable us to introduce excess polyamine into cells diacetly derivatives of多胺合成并检查。发现二乙酰戊胺是多胺摄取系统和多胺氧化酶的良好底物，然后有效地转化为HTC细胞中的精子定或非植物。但是，这些化合物并未成功地将其累积到异常的积累水平，这表明不利用多胺传输系统的SRTUCTURE使该化合物在细胞中积累至过量水平。