Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells.
Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells.
复制标题
神经生长因子在 PC12 大鼠嗜铬细胞瘤细胞中快速诱导鸟氨酸脱羧酶 mRNA。
DOI：
10.1073/pnas.82.17.5761
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发表时间：
1985
影响因子：
11.1
通讯作者：
Coffino,P
中科院分区：
文献类型：
--
作者：
Feinstein,SC;Dana,SL;McConlogue,L;Shooter,EM;Coffino,P
研究了神经生长因子 (NGF) 刺激大鼠嗜铬细胞瘤细胞系 PC12 中鸟氨酸脱羧酶 (OrnDCase；EC 4.1.1.17) 活性的机制。如前所述，NGF 以剂量依赖性方式快速诱导 OrnDCase 活性，在接触 NGF 后 4-6 小时酶活性达到最大。随后活动恢复到接近基础水平。使用克隆的 OrnDase cDNA 分析 OrnDase RNA 的水平。作为对 NGF 施用的反应，OrnDase RNA 水平被诱导。 OrnDCase RNA 诱导的时间进程与酶活性诱导的时间进程平行，并且两种诱导的幅度在数量上相同。在最早检查的时间点（2 小时）清楚地检测到 OrnDase RNA 浓度增加。 OrnDase RNA 的大小没有观察到变化。 RNA 和酶活性诱导的剂量反应曲线也相似。因此，增加的 OrnDase RNA 水平完全解释并负责活性的诱导。此外，三分之一的 OrnDCase RNA 诱导不受放线菌酮处理的影响，但被放线菌素 D 处理完全阻断，表明 NGF 通过至少两种机制介导 OrnDCase 诱导。第一种机制是放线菌酮不敏感，第二种机制是通过需要持续蛋白质合成的事件介导的。两种机制都需要持续转录，诱导过程对放线菌素 D 的完全敏感性证明了这一点。
The mechanism by which nerve growth factor (NGF) stimulates ornithine decarboxylase (OrnDCase; EC 4.1.1.17) activity in the rat pheochromocytoma cell line PC12 was investigated. As demonstrated previously, NGF rapidly induces OrnDCase activity in a dose-dependent manner, with maximal enzymatic activity at 4-6 hr after exposure to NGF. Activity subsequently returns to near basal levels. A cloned OrnDCase cDNA was used to analyze the levels of OrnDCase RNA. In response to NGF administration, OrnDCase RNA levels were induced. The time course of the OrnDCase RNA induction paralleled that of the enzyme activity induction, and the magnitude of both inductions was quantitatively the same. Increased concentration of OrnDCase RNA was clearly detected at the earliest time point examined, 2 hr. No change was observed in the size of OrnDCase RNA. The dose-response curves for both RNA and enzyme activity inductions were also similar. Thus, increased OrnDCase RNA levels fully account for, and are responsible for, the induction of activity. Further, one-third of the OrnDCase RNA induction was unaffected by cycloheximide treatment but was fully blocked by actinomycin D treatment, suggesting that NGF acts through at least two mechanisms to mediate the OrnDCase induction. The first mechanism is cycloheximide insensitive and the second is mediated through an event requiring ongoing protein synthesis. Both mechanisms require ongoing transcription, as evidenced by the complete sensitivity of the induction process to actinomycin D.