Regulation of S-adenosylmethionine decarboxylase by polyamines in Ehrlich ascites-carcinoma cells grown in culture.
Regulation of S-adenosylmethionine decarboxylase by polyamines in Ehrlich ascites-carcinoma cells grown in culture.
复制标题
多胺对艾利希腹水癌细胞中 S-腺苷甲硫氨酸脱羧酶的调节。
作者：
L. Alhonen
1.在悬浮培养中生长的埃利希腹水肿瘤细胞中研究了鸟氨酸脱羧酶（EC 4.1.1.50）抑制剂（即dl-α-二氟甲基鸟氨酸、1，3-二氨基丙烷和1，3-二氨基丙烷-2-醇）刺激S-腺苷4.1.1.17）活性的机制。2.二氟甲基鸟氨酸和二氨基丙烷，虽然减少腐胺和亚精胺的含量，显着刺激腺苷甲硫氨酸脱羧酶活性后，暴露的细胞的药物为8小时，而二氨基丙醇的效果只变得明显许多小时后。在肿瘤细胞暴露于任何的抑制剂，腺苷甲硫氨酸脱羧酶的活性和亚精胺和/或亚精胺加精胺的细胞内浓度之间存在密切的负相关性，这表明较高的多胺的消耗引发腺苷甲硫氨酸脱羧酶活性的增强。3.二氟甲基鸟氨酸和二氨基丙烷诱导的腺苷甲硫氨酸脱羧酶刺激的机制涉及（a）酶的表观半衰期显著增加和（B）诱导酶合成增强。二氨基丙醇似乎仅通过诱导机制起作用。4.二氟甲基鸟氨酸引起的腺苷甲硫氨酸脱羧酶活性的增加，可以通过外源亚精胺和精胺的微摩尔浓度在4 h内和腐胺在22 h内恢复到对照值。除了天然的多胺，腺苷甲硫氨酸脱羧酶活性升高可以被3，3 '-亚氨基二丙胺（亚精胺的类似物）抑制，但不能被非生理性二胺抑制。5.添加亚精胺和放线菌素D与二氟甲基鸟氨酸处理的培养物产生了可比的衰减增强腺苷甲硫氨酸脱羧酶活性（具有约2.5小时的表观半衰期），而放线菌酮的效果要快得多。本研究结果表明，多胺可以调节腺苷甲硫氨酸脱羧酶在基因表达的转录水平。
1. The mechanism of stimulation of S-adenosylmethionine decarboxylase (EC 4.1.1.50) activity by inhibitors of ornithine decarboxylase (EC 4.1.1.17), namely dl-alpha-difluoromethylornithine, 1,3-diaminopropane and 1,3-diaminopropan-2-ol, was studied in Ehrlich ascites-tumour cells grown in suspension cultures. 2. Difluoromethylornithine and diaminopropane, although decreasing the content of putrescine and spermidine, markedly stimulated adenosylmethionine decarboxylase activity after exposure of the cells to the drugs for 8h, whereas the effect of diaminopropanol only became apparent many hours later. In tumour cells exposed to any of the inhibitors, a close negative correlation existed between the activity of adenosylmethionine decarboxylase and the intracellular concentration of spermidine and/or spermidine plus spermine, suggesting that a depletion of higher polyamines triggered enhancement of adenosylmethionine decarboxylase activity. 3. The mechanism of difluoromethylornithine- and diaminopropane-induced stimulation of adenosylmethionine decarboxylase involved (a) a marked increase in the apparent half-life of the enzyme and (b) an induction of enhanced enzyme synthesis. Diaminopropanol seemed to act solely via an induction mechanism. 4. The increased adenosylmethionine decarboxylase activity elicited by difluoromethylornithine could be restored to control values by micromolar concentrations of exogenous spermidine and spermine in 4h and by putrescine in 22h. In addition to the natural polyamines, elevated adenosylmethionine decarboxylase activity could be repressed by 3,3'-iminodipropylamine, a close analogue of spermidine, but not by non-physiological diamines. 5. Addition of spermidine and actinomycin D to cultures treated with difluoromethylornithine produced a comparable decay of enhanced adenosylmethionine decarboxylase activity (with an apparent half-life of about 2.5h), whereas the effect of cycloheximide was much more rapid. The present results suggest that polyamines may regulate adenosylmethionine decarboxylase at the transcriptional level of gene expression.