Cycloheximide protection against actinomycin D cytotoxicity.
Cycloheximide protection against actinomycin D cytotoxicity.
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放线菌酮可防止放线菌素 D 细胞毒性。
DOI：
10.1002/jcp.1041530310
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发表时间：
1992
影响因子：
5.6
通讯作者：
Soprano,KJ
中科院分区：
文献类型：
--
作者：
Borrelli,MJ;Stafford,DM;Rausch,CM;Ofenstein,JP;Cosenza,SC;Soprano,KJ
预处理加放线菌酮（10 μg/ml）处理可保护中国仓鼠卵巢细胞和Swiss 3 T3细胞免受放线菌素D的细胞毒性。放线菌酮处理通过降低放线菌素D结合到细胞的酸可沉淀部分的水平来降低放线菌素D的细胞内浓度。放线菌素D未结合的水平不受放线菌酮的影响，表明AD的质膜渗透性没有降低。放线菌素D抑制总转录，但未降低rRNA和大多数检测mRNA的细胞质水平;然而，c-myc mRNA的细胞质水平降低至检测限以下。放线菌酮治疗进一步抑制总转录，并没有影响rRNA的细胞质水平，也没有大多数测试的mRNA。放线菌酮使c-myc的细胞质水平升高，即使在放线菌素D的存在下也保持如此。这些数据表明，细胞质中短寿命必需mRNA（如c-myc mRNA）水平的降低是放线菌素D的一种致死性病变。此外，放线菌酮的保护作用可能部分来自其稳定和/或提高这些mRNA的细胞质水平的能力，从而抵消放线菌素D对它们的消耗。放线菌酮诱导的放线菌素D与细胞酸可沉淀部分结合的减少也可能导致保护作用。© 1992 Wiley利斯公司
Pretreatment plus concomitant treatment with 10 μg/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c‐myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c‐myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c‐myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide‐induced reduction of actinomycin D bound to the acid precipitable fraction of the cells. © 1992 Wiley‐Liss, Inc.