Dicyclohexylamine effects on HTC cell polyamine content and ornithine decarboxylase activity.
Dicyclohexylamine effects on HTC cell polyamine content and ornithine decarboxylase activity.
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二环己胺对 HTC 细胞多胺含量和鸟氨酸脱羧酶活性的影响。
DOI：
10.1016/0304-4165(85)90210-7
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Qasba,P
中科院分区：
文献类型：
--
作者：
Mitchell,JL;Mahan,DW;McCann,PP;Qasba,P
二环己胺，亚精胺合酶抑制剂，其能力进行了评估，以改变特定的多胺水平在大鼠肝癌HTC细胞培养。0.5和1.0 mM的培养基浓度减少了从腐胺的亚精胺的生产，并提高了现有的亚精胺到精胺的转化。这在多胺水平中产生了非常有趣的变化，使得在24小时后腐胺含量几乎是对照值的3倍，精胺是约2倍，而亚精胺降低至对照培养物的约10%。这种模式的多胺是非常不同的常见的多胺生物合成抑制剂，如甲基乙二醛双（鸟苷酰腙）和二氟甲基鸟氨酸诱导和复制的模式诱导的S-腺苷-1，8-二氨基-3-硫代辛烷，过渡态类似物设计为一个特定的亚精胺合酶抑制剂。当细胞被血清刺激时，二环己基胺的存在引起了非常大的诱导，尽管在鸟氨酸脱羧酶的异常高水平的腐胺和精胺。伴随的抑郁症的亚精胺水平诱导的4倍增加，这种酶的稳定性，可以通过添加外源亚精胺逆转。这些数据表明，亚精胺诱导，也许在转录水平上，蛋白质，这是必要的特征非常迅速的失活的鸟氨酸脱羧酶。
Dicyclohexylamine, a spermidine synthase inhibitor, was evaluated for its ability to alter specific polyamine levels in rat hepatoma HTC cells in culture. Media concentrations of 0.5 and 1.0 mM reduced the production of spermidine from putrescine and enhanced the conversion of existing spermidine to spermine. This created a very interesting change in polyamine levels such that after 24 h putrescine content was almost 3-times control values and spermine was about twice, while spermidine was lowered to about 10% of control cultures. This pattern of polyamines is quite distinct from that induced by the common polyamine biosynthetic inhibitors like methylglyoxal bis(guanylhydrazone) and difluoromethylornithine and replicates the pattern induced byS-adenosyl-1,8-diamino-3-thiooctane, a transition-state analog designed as a specific inhibitor of spermidine synthase. When cells were stimulated by serum addition, the presence of dicyclohexylamine caused an extraordinarily large induction in ornithine decarboxylase in spite of the abnormally high levels of both putrescine and spermine. The concomitant depression of spermidine levels induced a 4-fold increase in the stability of this enzyme that could be reversed by the addition of exogenous spermidine. The data suggest that spermidine induces, perhaps at the transcriptional level, a protein that is necessary for the characteristically very rapid inactivation of ornithine decarboxylase.