Summers J M, Hawkins S E
J Cell Sci. 1978 Apr;30:237-50. doi: 10.1242/jcs.30.1.237.
Antrycide is an aminoquinaldine whose inhibitory action on the growth of Trypanosoma and Crithidia is not fully understood at the cellular level. The growth of Amoeba discoides in concentrations of antrycide between 0.5 and 2 microgram/ml was reduced considerably, while cells failed to divide in 4 microgram/ml. The effects on growth rate were reversible at least up until 7 days in antrycide. In order to assess the action of this synthetic drug on RNA synthesis in amoebae, the pattern of synthesis in normal cells was investigated using polyacrylamide gel electrophoresis. The profile of high molecular weight RNAs observed depended on the length of time in [3H]uridine, and was only fully developed after 66 h, when 5 peaks could be seen. The relative molecular weights of these peaks (I--V) were 2.45, 1.55, 1.13, 0.8 and 0.52 X 10(6) Daltons respectively. Those of 1.55 and 0.8 X 10(6) corresponded to ribosomal RNAs, the identity of the other peaks is unknown. After growth in 2 microgram/ml antrycide for 4 days, no high molecular weight RNA was found. Use of [14C]adenine/[3H]uridine showed that after 17 h in antrycide there was a loss of ribosomal RNA and increased levels of low molecular weight RNAs, due either to lack of synthesis or to degradation of newly synthesized material. Incorporation of [3H]leucine into hot acid-precipitable protein was inhibited in antrycide-treated cells by at least 50%. A possible explanation of the effect of antrycide on A. discoides was the inhibition of mRNA synthesis for ribosomal proteins, leading to degradation of newly synthesized rRNA. Reduced growth would continue on pre-existing ribosomes and previously synthesized long-lived mRNAs.
安锥赛是一种氨基喹哪啶,其对锥虫和短膜虫生长的抑制作用在细胞水平上尚未完全明确。在浓度为0.5至2微克/毫升的安锥赛中,盘状阿米巴的生长显著减缓,而在4微克/毫升时细胞无法分裂。至少在长达7天的安锥赛作用时间内,对生长速率的影响是可逆的。为了评估这种合成药物对阿米巴RNA合成的作用,使用聚丙烯酰胺凝胶电泳研究了正常细胞中的合成模式。观察到的高分子量RNA图谱取决于在[3H]尿苷中的孵育时间,并且只有在66小时后才完全显现,此时可以看到5个峰。这些峰(I - V)的相对分子量分别为2.45、1.55、1.13、0.8和0.52×10⁶道尔顿。其中1.55和0.8×10⁶对应的是核糖体RNA,其他峰的身份未知。在2微克/毫升的安锥赛中生长4天后,未发现高分子量RNA。使用[14C]腺嘌呤/[3H]尿苷表明,在安锥赛中孵育17小时后,核糖体RNA减少,低分子量RNA水平升高,这要么是由于缺乏合成,要么是由于新合成物质的降解。在经安锥赛处理的细胞中,[3H]亮氨酸掺入热酸沉淀蛋白的过程至少被抑制了50%。安锥赛对盘状阿米巴产生作用的一种可能解释是,它抑制了核糖体蛋白的mRNA合成,导致新合成的rRNA降解。生长减缓将在预先存在的核糖体和先前合成的长寿命mRNA上持续。