Raina A, Tuomi K, Pajula R L
Biochem J. 1982 Jun 15;204(3):697-703. doi: 10.1042/bj2040697.
5'-Methylthioadenosine and four 5'-alkylthiotubercidins were tested for their ability to inhibit polyamine synthesis in vitro and to decrease polyamine concentration and prevent growth of baby-hamster-kidney (BHK21) cells. 5'-Methylthioadenosine and 5'-methylthiotubercidin decreased the activity of spermidine synthase from brain to roughly the same extent, whereas brain spermine synthase was much more strongly inhibited by 5'-methylthioadenosine compared with 5'-methylthiotubercidin. These nucleoside derivatives also inhibited the growth of BHK21 cells and increased the concentration of putrescine. 5'-Methylthioadenosine decreased cellular spermine concentration, whereas 5'-methylthiotubercidin lowered the concentration of spermidine. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were enhanced in cells grown in the presence of 5'-methylthiotubercidin. The growth inhibition produced by these nucleoside derivatives was not reversed by exogenous spermidine or spermine. 5'-Ethylthiotubercidin, 5'-propylthiotubercidin and 5'-isopropylthiotubercidin did not appreciably inhibit spermidine or spermine synthase in vitro or decrease the cellular polyamine content, but effectively prevented the growth of BHK21 cells. All nucleoside derivatives at concentrations of 0.2-1 mm caused a rapid inhibition of protein synthesis. It is concluded that the growth inhibition produced by 5'-methylthioadenosine and 5'-alkylthiotubercidins was not primarily due to polyamine depletion but other target sites, for instance the cellular nucleotide pool, cell membranes etc. must be considered.
对5'-甲硫基腺苷和四种5'-烷基硫代结核菌素进行了测试，以考察它们在体外抑制多胺合成、降低多胺浓度以及阻止幼仓鼠肾（BHK21）细胞生长的能力。5'-甲硫基腺苷和5'-甲基硫代结核菌素对脑内亚精胺合酶活性的抑制程度大致相同，而与5'-甲基硫代结核菌素相比，5'-甲硫基腺苷对脑内精胺合酶的抑制作用要强得多。这些核苷衍生物还抑制了BHK21细胞的生长，并增加了腐胺的浓度。5'-甲硫基腺苷降低了细胞内精胺的浓度，而5'-甲基硫代结核菌素则降低了亚精胺的浓度。在5'-甲基硫代结核菌素存在下生长的细胞中，鸟氨酸脱羧酶和S-腺苷甲硫氨酸脱羧酶的活性增强。这些核苷衍生物产生的生长抑制作用不能被外源性亚精胺或精胺逆转。5'-乙硫基结核菌素、5'-丙硫基结核菌素和5'-异丙硫基结核菌素在体外对亚精胺或精胺合酶没有明显抑制作用，也没有降低细胞内多胺含量，但能有效阻止BHK21细胞的生长。浓度为0.2 - 1 mM的所有核苷衍生物都能迅速抑制蛋白质合成。得出的结论是，5'-甲硫基腺苷和5'-烷基硫代结核菌素产生的生长抑制作用主要不是由于多胺耗竭，而是必须考虑其他靶位点，例如细胞核苷酸池、细胞膜等。
