Jones R E, Moscona A A
J Cell Biol. 1977 Jul;74(1):30-42. doi: 10.1083/jcb.74.1.30.
Cytosine arabinoside (Ara-C) elicits a significant increase in the level of the enzyme glutamine synthetase (GS) while it markedly reduces overall RNA and protein synthesis in cultures of embryonic chick neural retina. This increase was analyzed by radioimmunochemical procedures and compared with the induction of GS by hydrocortisone (HC). Accumulation of GS in Ara-C-treated retinas was found to be due to de novo synthesis of the enzyme; however, unlike the induction of GS by HC, Ara-C caused no measurable increase in the rate of GS synthesis. The results indicate that Ara-C facilitates GS accumulation largely by preventing degradation of the enzyme. Even though Ara-C inhibits the bulk of RNA synthesis in the retina, it does not stop the formation of GS-specific RNA templates. However, the progressive accumulation of these templates does not result in an increased rate of GS synthesis unless Ara-C is withdrawn from such cultures under suitable experimental conditions. Thus, it is suggested that the continuous presence of Ara-C imposes a reversible hindrance at the translational level which limits the rate of GS synthesis. The results demonstrate that the increase in retinal GS elicited by Ara-C is achieved through mechanisms which are quite different from those involved in the hydrocortisone-mediated induction of this enzyme.
阿糖胞苷（Ara-C）可使胚胎鸡神经视网膜培养物中的谷氨酰胺合成酶（GS）水平显著升高，同时显著降低总体RNA和蛋白质合成。通过放射免疫化学方法分析了这种升高，并与氢化可的松（HC）诱导的GS进行了比较。发现在经Ara-C处理的视网膜中GS的积累是由于该酶的从头合成；然而，与HC诱导GS不同，Ara-C并未使GS合成速率出现可测量的增加。结果表明，Ara-C主要通过防止该酶的降解促进GS积累。尽管Ara-C抑制视网膜中的大部分RNA合成，但它并未阻止GS特异性RNA模板的形成。然而，除非在合适的实验条件下从这种培养物中去除Ara-C，否则这些模板的逐渐积累不会导致GS合成速率增加。因此，有人提出Ara-C的持续存在在翻译水平上施加了一种可逆的阻碍，从而限制了GS合成的速率。结果表明，Ara-C引起的视网膜GS升高是通过与氢化可的松介导的该酶诱导所涉及的机制截然不同的机制实现的。
