Induction of spermidine/spermine N1-acetyltransferase activity in Chinese-hamster ovary cells by N1N11-bis(ethyl)norspermine (corrected) and related compounds.
Induction of spermidine/spermine N1-acetyltransferase activity in Chinese-hamster ovary cells by N1N11-bis(ethyl)norspermine (corrected) and related compounds.
复制标题
N1N11-双（乙基）去甲精胺（已校正）和相关化合物诱导中国仓鼠卵巢细胞中的亚精胺/精胺 N1-乙酰转移酶活性。
DOI：
10.1042/bj2670331
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Bergeron,RJ
中科院分区：
文献类型：
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作者：
Pegg,AE;Pakala,R;Bergeron,RJ
用N1N11-双(乙基)去甲精胺(BENSM)处理中国仓鼠卵巢(CHO)细胞，导致亚精胺/精胺N1-乙酰转移酶(SAT)的活性大幅增加，在48小时内增加了约600倍。 3,7,11,15,19-五氮杂十六烷、N1N12-双(乙基)精胺和N1N14-双(乙基)高精胺也按效力降序产生较小但仍然非常大的增加。使用针对大鼠肝脏 SAT 的抗体进行免疫印迹表明，乙酰转移酶活性的升高是由于酶蛋白的增加。 SAT mRNA 含量增加，表明 BENSM 部分通过改变 mRNA 的转录或稳定性来调节酶蛋白水平。用该药物处理的 CHO 细胞中蛋白质的降解率也有所降低。这可能是由于 BENSM 的结合所致，BENSM 是该酶的竞争性抑制剂，Ki 为 120 microM。暴露于BENSM导致亚精胺向N1-乙酰亚精胺和腐胺的转化增加，细胞内多胺的含量迅速下降以及腐胺、N1-乙酰亚精胺和亚精胺从细胞中的排泄。当处理细胞中的多胺氧化酶活性被阻断时，N1-乙酰亚精胺和N1-乙酰精胺的增加量更大，并且腐胺的形成被阻止。这些结果表明，SAT 的诱导促进精胺和亚精胺降解为腐胺以及随后从细胞中排泄腐胺。当多胺氧化酶对 N1-乙酰基衍生物的降解被阻断时，细胞会分泌 N1-乙酰基亚精胺而不是腐胺。 CHO 细胞还含有并分泌 N8-乙酰亚精胺，但在用 BENSM 处理的细胞中其合成并未增加，这证实了体外获得的数据，SAT 不产生这种衍生物。
Treatment of Chinese-hamster ovary (CHO) cells with N1N11-bis(ethyl)norspermine (BENSM) led to a very large increase in the activity of spermidine/spermine N1-acetyltransferase (SAT), which rose by about 600-fold within 48 h. Smaller, but still very large increases, were also produced in decreasing order of potency by 3,7,11,15,19-penta-azaheneicosane, N1N12-bis(ethyl)spermine and by N1N14-bis(ethyl)homospermine. The rise in acetyltransferase activity was due to an increase in enzyme protein, as indicated by immunoblotting using antibodies directed against rat liver SAT. There was an increase in the content of mRNA for SAT, indicating that BENSM regulates the level of enzyme protein partly by means of a change in transcription or stability of the mRNA. There was also a decreased rate of degradation of the protein in CHO cells trated with the drug. This may be due to the binding of BENSM, which is a competitive inhibitor of the enzyme with a Ki of 120 microM. Exposure to BENSM led to an increased conversion of spermidine into N1-acetylspermidine and putrescine, a rapid fall in the content of intracellular polyamines and the excretion from the cell of putrescine, N1-acetylspermidine and spermidine. When polyamine oxidase activity in the treated cells was blocked, increases in N1-acetylspermidine and N1-acetylspermine were much greater, and the formation of putrescine was prevented. These results indicate that the induction of SAT facilities the degradation of spermine and spermidine to putrescine and the subsequent excretion of putrescine from the cell. When the degradation of the N1-acetyl derivatives by polyamine oxidase is blocked, the cells excrete N1-acetylspermidine instead of putrescine. CHO cells also contained and excreted N8-acetylspermidine, but its synthesis was not increased in cells treated with BENSM, confirming data obtained in vitro that SAT does not produce this derivative.