Structural and functional relationship among diamines in terms of inhibition of cell growth

Structural and functional relationship among diamines in terms of inhibition of cell growth
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DOI:
10.1093/jb/mvh150
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发表时间:
2004-10-01
影响因子:
2.7
通讯作者:
Igarashi, K
Igarashi, K
中科院分区:
生物学4区
文献类型:
--
作者:
Higashi, K;Yoshida, K;Igarashi, K

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根据胍丁胺通过诱导抗酶而对细胞生长具有抗增殖作用的报道[萨特里亚诺等(1998)J.Biol.Chem.273,15313 -15316],我们检测了16种不同的二胺对细胞生长的作用。许多二胺对细胞生长几乎没有影响,但胍丁胺和1,6-己二胺具有抗增殖作用,胍丁胺的作用最强。细胞生长抑制发生在2天后,抑制作用的程度的抗酶诱导。精胺水平的降低表明,诱导亚精胺/精胺N-1-乙酰转移酶也参与了胍丁胺和1,6-己二胺对细胞生长的抑制。在兔网织红细胞无细胞系统中测定的移码效率(有或没有移码的抗酶合成的比率)也增加了1,3-丙二胺和顺式-1,4-环己二胺,除了胍丁胺和1,6-己二胺。然而,当将这些化合物添加到细胞培养基中时,1,3-丙二胺和顺式-1,4-环己二胺的细胞内水平较低。其他二胺对细胞生长或移码效率没有影响。结果表明,两个氨基的存在下,由一个适当的距离分开的是重要的增强移码二胺。
Following the report that agmatine has an anti-proliferative effect on cell growth through induction of antizyme [Satriano et al. (1998) J. Biol. Chem. 273,15313-15316], we examined the effects of 16 different diamines on cell growth. Many diamines had little or no effect on cell growth, but agmatine and 1,6-hexanediamine had anti-proliferative effects, with agmatine having the strongest effect. Inhibition of cell growth occurred after 2 days, and inhibitory effects paralleled the degree of antizyme induction. Decreased spermine levels indicated that induction of spermidine/spermine N-1-acetyltransferase was also involved in the inhibition of cell growth by agmatine and 1,6-hexanediamine. The frameshift efficiency (ratio of antizyme synthesis with or without frameshift) measured in a rabbit reticulocyte cell-free system was also increased by 1,3-propanediamine and cis-1,4-cyclohexanediamine in addition to agmatine and 1,6-hexanediamine. However, the intracellular levels of 1,3-propanediamine and cis-1,4-cyclohexanediamine were low when these compounds were added to the cell-culture medium. Other diamines had no effect on cell growth or frameshift efficiency. The results suggest that the presence of two amino-groups separated by an appropriate distance is important for the enhancement of frameshifting by diamines.